NYUCD General Embryology

Embryonic Period
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• During the 4th week PGCs migrate from the yolk sac towards the genital ridge(genital ridge) so orginaly
• PGCs migrate along the gut tube and the dorsal mesentery

[4th week (PGC move back into the embryo from yolk sack toward the tissue where it will host (genital ridge) so originally PGC are located in the back "posterior" and they will migrate along the digestive tract "hindgut" all the way to the genital
ridge ** while migrading they will proliferate""]
Primitive Sex Cordsformed when the epithelium of the genital ridge proliferates into the underlying mesenchyme when PGCs arrive @ male Migrating PGC --> male genital ridge --> SRY GENE --> TESTIS @ female Migrating PGCs --> female genital ridge --> default pathway --> ovary (no SRY gene) o If SRY gene is not activated --> gonad will be ovary because that is the default pathway when SRY gene is not presentGENETICALLY MALE EMBYROS- Genetically male embryos have an XY sex chromosome complex - The Y chromosome carry SRY gene, the testis-determining factor >>Determine whether the gonad will differentiate towards the testes >>SRY GENE: DETERMINING FACTOR OF WHETHER YOU MAKE MALE OR FEMALE GONAD - Under the influence of SRY the primitive sex cords differentiate into medullary/testis cords --> TestisGENETICALLY FEMALE EMBRYOS- Genetically female embryos have an XX sex chromosome complex - In the absence of SRY function the primitive sex cords degenerate - The surface epithelium proliferate to give rise to cortical cords --> OvaryMeiosiso A unique division process, which occurs exclusively in germ cells o Consists of 2 successive meiotic divisions: Meiosis I & Meiosis II o Reduction of the number of chromosome to a haploid number of 23Function of Meiosis- Meiotic recombination 2 rounds - Reduction of the number of chromosomes to a haploid complementKey Events in Meiosis1. One round of (pre-meiotic) DNA replication 2. A unique Prophase I stage of meiosis for genetic exchange (important for recombination) 3. Two rounds of chromosome segregation, Meiosis I & Meiosis II (divide chromosomes to their appropriate contents) >>>The initiation of meiosis marks the transition from PGC to gameteMitosiso Cell division giving rise to 2 daughter cells that are genetically identical o Each cell receives the complete complement of 46 chromosomes - Chromosomes are replicated during interphase -Mitosis starts during prophase --> chromosomes that are duplicated will line up at equator of cell (metaphase plate) --> chromosomes separated during anaphase and give rise to two daughter cells identical to motherChiasmaprocess where genetic information is exchangedMeiotic Recombinationgenetic exchange between maternal & paternal allelesLED ZEPPLIN PLAYS the DRUMSPROPHASE OF MEIOSIS I - leptotene - zygotene - pachytene - diploteneLeptoteneCondensation of chromosomesZygotenePairing/synapsis of homologous chromosomesPachyteneCrossing-over/meiotic recombinationàexchange of section of chromosome from adjacent chromosomesDiploteneSynapsed chromosomes begin to separateProduction of gametes in female and maleo Both go through rounds of mitotic division --> give rise to haploid cells o Male: single spermatocyte --> 4 mature spermatids (gametes) that are identical o Female: one mature gamete: >>1 cell normal in size and gets most of the cytoplasm >>3 cells smaller in size, less cytoplasm: POLAR BODIESGerm cell development in the male genital ridge- Germ cells are committed to spermatogenesis - Sertoli cells have differentiated and testis cords have formed - Germ cells enter mitotic arrest - forming spermatogonia - Mitosis is not resumed until after birth o First Meiotic division is initiated at pubertyGerm cell development in the female genital ridge- Germ cells are committed to oogenesis >>All germ cells synchronously enter meiotic prophase and become oocytes - Undergo the early stages of meiosis (meiotic recombination) - Oocytes arrest at diplotene prophase I at the time of birth - First Meiotic division is completed at puberty (PGCs)OogenesisProcess by which oogonia differentiate into mature oocytes - PCGS --> oogonia ( at the gonad 6 weeks) --> MITOSIS --> primary oocytes ( arrested division at prophase) - Primary oocytes surrounded by follicular epithelial cells = primordial follicles - Primordial follicle with the growing primary oocyte --> granulosa cells --> primary follicles ( at puberty) - Primary oocytes surrounded by zona pellucida - Primary oocytes + zona pellucida --> secondary oocyte - Primary oocyte develops antrum (fluid filled cavity) --> - Antrum + granulosa cells surrounding primary oocyte= cumulus oophorus ** Primordial follicle: primary oocyte + follicular epithelial cells ** Primary follicle: primary oocyte + granulosa cells ( proliferated follicular cells) + -Primary oocyte + zona pellucida --> necessary for fertilization ** secondary follicle: primary oocyte with antrum ( fluid filled space) ** EVENT 1: Mitosis begins at 6 weeks --> Meiosis I begins at BIRTH ** meiosis I is arrested at prophases & completed upon LH hormone stimulation at PUBERTY ( in males Meiosis I begins at puberty) ** Meiosis II is arrested at metaphase & completed upon fertilization ** Ovulation takes place BETWEEN metaphase arrest in MEIOSIS II & fertilizationZona pellucida- glycoprotein layer - important recognition of sperm and oocyteSpermatogenesiso The process by which spermatogonia are transformed into spermatozoa ( mature ) - It begins at puberty ( Meiosis I in seminiferous tubules) and continues into old age. - Meiosis and sperm maturation begins at puberty in the seminiferous tubules - Self renewing, mitotic, spermatogonial stem cell population (continuous process) - Continuously divide during life of individual spermatoginia > Mitosis >Primary spermatocytes --> Meiosis I --> Secondary spermatocytes --> Meiosis II --> Spermatids 1 spermatogonia --> 4 mature spermatids - spermatogonia= diploid - primary spermatocyte= product of mitosis - secondary spermatocyte= product of meiosis I ( diploid) - early spermatid = product of meiosis II ( haploid) FROM SPERMATID --> SPERM ( MATURATION) >>>Acrosome formation >>>Condensation of the nucleus o nucleus reduced in size >>>Loss of cytoplasm: phagocytized by SERTOLI CELLS >>>Middle piece >>>tail formationFertilizationo Fertilization is the fusion of haploid gametes, egg and sperm (spermatozoa and oocytes) o Results in the formation of the diploid embryo o the beginning of embryogenesisFERTILIZATION occurs inampullary region of the fallopian tube and involves: a small fraction of sperm that continues on to meet oocyteKey Features of Fertilization 1: Capacitation of the sperma. conditioning of the sperm in the female reproductive tract b. sperm by itself has no capacity in fertilizing egg, unless it is sustained in female tract for about 7 hours (uterine wall and follicle tube are conditions that make it possible to fertilize egg)Key Features of Fertilization 2: Contact and recognitiona. binding to species-specific receptors on the zona pellucida (ZP3) b. zona pellucida will secrete a different combination of protein called ZP3 allowing sperm to bind to oocyteKey Features of Fertilization 3: Acrosome reactiona. release of proteolytic enzymes to digest the zona pellucida b. acrosome: head of sperm which contains a lot of proteolitic enzymes which is essential for digesting the zona pellucida protecting the oocyteKey Features of Fertilization 4:a. cortical granule reaction in the egg - block to polyspermy b. only nucleus of the sperm enters the cytoplasm of the oocyteKey Features of Fertilization 5: Egg activationcompletion of meiosis II (second meiotic division)Key Features of Fertilization 6: Fusion of the genetic materialformation of the diploid embryo (zygote)- sperm and egg fuseCORTICAL GRANULE REACTION** occurs during fusion of the egg membrane & sperm nucleus** - prevents any other sperm from entering oocyte= preventspolyspermy - cortical granules surround the membrane of the eggsperm releases proteolytic enzyme from acrosome --> dissolves zona pellucida --> membrane of the sperm fuses with memebrane of egg --> Cortical granules fuse with membrane of oocyte and release the contents of the granules into perivitelline space ( space created by the detachement of the oocyte membrane from the zona pellucida) --> this creates an additional space between oocyte membrane and zona pellucida that PREVENTS the entry of another sperm ** product of fertilization= ZYGOTE ( 2 polar bodies, zona pellucida + diploid genetic material)CLEAVAGEZygote undergoes a series of mitotic divisions - o Cells after mitotic division (cleavage) are called blastomeres o Cells go from 2-4 to 8 cells stage o Cleavage ends upon formation of blastulaWhat regulates development?Initiation of gene transcription from the embryonic genome that will regulate subsequent development ** FERTILIZED ZYGOTE --> 8-CELL ( cleavage) --> MORULA ( builds up in fluid --> BLASTOCYST (once the blastocoel forms)EMBRYONIC GENOME ACTIVATIONBefore fertilization: regulation depends on maternal mRNA so: 1) Degradation of maternal mRNAs (Maternal mRNA degrades when sperm invades) 2) minor zygomatic genome activation (ZGA) 3) Major ZGA >>> ZGA: essential for regulating subsequent development of embryoCOMPACTION ( 8 cell stage)o Occurs during 3rd day of fertilization o Around the 8-cell stage the embryo goes through the process of compaction o Function of compaction: blastomeres maximize their contact with each other > maximize contact between each blastomereCellular events associated with compaction§ Increase in tight junction formation § Production of E-cadherin (cell-cell adhesion molecule) § Increase cell contact between all the cells § Formation of gap junctions § Shape change in outer blastomeres § Inner/outer polarity in cells (predicts inner/outer polarity of the embryo) § Some cells will stay inside membrane and some will be outsideBlastocytesform within embryo itself (have outer and inner cells) -->location will determine fate of cell typesBlastocele(cavity) forms progressively through build up of fluid inside the morulaTROPHOECTODERMFormed by blastomeres remaining in contact with the outside TROPHOECTODERM= PLACENTA "outside is the winner & wins a trophy" > trophoblast + ectoderm= trophoectodermEMBRYO PROPERFormed by blastomeres inside the embryo: inner cell mass (ICM) "Inner is humble & proper"Segregation of trophectoderm and ICM lineages depends ono EXPRESS OCT4 --> dictates embryo proper ( ICM) o EXPRESS CDX2 --> dictates placenta (trophoectoderm)INNER CELL MASS (ICM) = EMBRYO PROPER PROPERTIESo Source of Embryonic Stem Cells (ESCs) o Isolate cells and put them in culture --> have ability to proliferate and give rise to all tissueEmbryonic Stem Cells (ESCs)o ESCs can self-renew (unlimited division) o ESCs are pluripotent (express OCT4) o Can give rise to cell types from all three primary germ layersAfter implantation the ICM divides intoepiblast & hypoblastEpiblastgives rise to EMBRYO > Dependent on GATA6 transcription factorEpiblast derivativeso Ectoderm of amnion --> FORMS AMNIOTIC CAVITY! o Ectoderm of the embryo o Primitive streak: > Extra embryonic mesoderm > Embryonic mesoderm > Notochordal processes > Embryonic ENDODERMHypoblastgives rise to the LINING OF THE ENTIRE CAVITY > Dependent on NANOG transcription factorHypoblast Derivatives- give rise to yolk sac and lining (everything extra) - Doesn't contribute to embryo proper - Endoderm of yolk sac --> EXTRAEMBRYONIC MESODERMEpiblast + Hypoblastform the BILAMINAR EMBYRONIC DISCCYTROTROPHOBLAST & SYNCHTIOTROPHOBLASTprovide attachment of uterine wallCYTROTROPHOBLAST(inner layer of trophoblast) penetrate maternal spiral arteries and route the blood flow through the placenta for the growing embryo to useSYNCHTIOTROPHOBLAST(outer layer of trophoblast) secretion of proteolytic enzymes which erode the endometrial epithelium and the stroma of the endometrium, so that the blastula can penetrate, and get implanted in the endometriumHATCHING FROM THE ZONA PELLUCIDAIMPORTANT FOR IMPLANTATION ( 4-5 days) - When the blastocyst reaches the uterus, it must 'hatch' from the zona pellucida in order to implant into the uterine wall - Trophoblast cells secrete proteases to digest the zona pellucida surrounding the BLASTOCYST ( developing embryo) - Once the blastocyte is RELEASED from the zona pellucida= HATCHING & the embyro is ready for implantation on the uterine wallhatching too earlyectopic pregnancyhatching doesn't occur regularlyfailed pregnancyBLASTOCYST IMPLANTATION5 1/2 - 6 days - Embryo will implant @ endometrium of uterine wall - Hypoblast segregates from ICM - Epiblast rest of ICM forms embryo - Amniotic Cavity appears in epiblast7.5 day human blastocyst- Implantation takes place in six or seven days - Inner cell mass: hypoblast and epiblast (blue) > Cavity within epiblast: amnionitic cavityo > Uterine wall; trophoblast start to invade uterine wall - Trophoblast derived from ectoderm9-day human blastocyte- Hypoblast: lines blastocyte cavity - Blood circulation from mother12-day human blastocyte- Hypoblast blast: gives rise to extraembryonic membrane - Blood from mother gives rise to lacunae13-day human blastocyste- Laminar disc: - Blastocyte is invading the uterine wall and in the cavity of uterine wall of mother Form primary villi essential in forming the placenta itselfSomatic cells-are the cells forming the body of an organism (tissues and organs), as opposed to the germline, which form the gametes (spermatozoa and oocyte). *are entirely derived from the three embryonic germ layers: ectoderm, mesoderm and endoderm - which are established during gastrulation.Germlineforms gametes (spermatozoa & oocyte)GASTRULATION & GERM LAYER FORMATION- A process characterized by profound cell movements that convert a sheet of cells into a multi-layered organism. *Bilaminar group of cells --> Multilayer organisms -One of consequences of this reorganization is that group of cells are brought in close contact to undergo inductive interactions. *Group of cells at a distance will come close in appositionMajor outcome of gastrulationis the formation of the three germ layers of the embryo. *Ectoderm, mesoderm and endodermPrimitive streak> give rise to a lot of cells of the three germ layers -Groove in which cells will invaginate into cavity -PRIMITIVE STREAK=GROOVE *Cells move into cavity (epithelium into mesenchymal transition) *Loose contact with enveloping cells and fold and enter cavity during the process *Cells will migrate from each site of the primitive streak and from the primitive node anteriorallyKey Events Associated with Gastrulation:- Epiblast cells forming the primitive streak migrate in an anterior position to form the node. - First cells passing through the primitive streak displace the cells of the hypoblast to give rise to the embryonic/definitive endoderm. - Cells at the node move anteriorly to form the head mesoderm and the notochord as the primitive streak regresses. - Cells moving through the primitive streak between the epiblast and the endoderm will form the embryonic mesoderm. - Epiblast cells that remain at the surface will form the embryonic ectoderm. - ECTODERM AND ENDODERM: derived from epiblast - MESODERM: axon of the notochordOropharyngeal Membrane-at the cranial end - will break down to form the stomodeum (mouth opening). *The most anterior part of embryo: juxtaposition of ectoderm and endoderm --> stomodeum, NO MESODERMFirst cells of notochordwill be layed down ANTERIORALLYCloacal Membrane-is at the caudal end - will break down to form the opening of the anus. *The most posterior part of the embryo: juxtaposition of ectoderm and endoderm, NO MESODERMDERIVATIVES OF THE ECTODERM-Ectoderm is the most superficial layer. *Epidermis *Sense organs *Central nervous system *Neural crest derivatives *Peripheral nervous system (neurons and glia) *Pigment cells *Craniofacial skeleton *Odontoblasts *Adrenal medullaNeural Inductionthe process by which neural plate is generated >Gastrulation: allow mesoderm to migrate right underneath ectoderm --> allow for inductive interaction to take placeInductive interaction between the chordamesoderm/notochord and the ectodermSignal derived from tissue induces the overlaying ectoderm to form neural plateMolecular Regulation of Neural Induction-The secreted molecule bone morphogenetic protein 4 (BMP4) expressed throughout the ectoderm regulates the decision between epidermal and neural fate * BMP4: promotes bone growthBMP4NO INHIBITION ectoderm into dermis - regulates the decision between epidermal and neural fate and it promotes bone growth - BMP4 will bind to its receptor, activated/secreted by ectoderm --> epidermal ectodermInhibition of BMP4ECTODERM into (anterior) neural plate or FOREBRAIN Inhibition of BMP4 signaling in the ectoderm is required to convert the ectoderm into neural tissue (mediated by the dorsal mesoderm)BMP4 antagonists- Noggin, Chordin and Follistatin - Are secreted by the dorsal mesoderm/notochord - They bind BMP4 molecules preventing BMP4 interaction with its receptorBMP4 antagonists + FGF/RETINOIC ACID/Wnt-3A(1) ACTIVATION: mesoderm secrete caudal antagonist (chordin, noggin, follstatin) (2) TRANSFORMATION: FGF, retinoic acid and Wnt-3a --> transformation of (posterior) neural plate = neural tube (pattern neural tissue from anterior-posterior)ACTIVATION:mesoderm secrete caudal antagonist (nogging, chordin, and follistatin)TRANSFORMATION:FGF, retinoic acid and Wnt-3a --> transformation of neural tissue with anterior-posterior character (pattern neural tissue from anterior-posterior)NeurulationThe process by which the neural plate folds into the neural tube.Neurulation results in the segregation of:the three ectodermal derivatives: -neural tube *(CNS-brain) -neural crest -epidermis (outer ectoderm)shaping:thickening of cells that form neural platefolding:neural plate starts to foldelevation:fold of neural plate starts to rise upclosure:tip of neural plate will fuse together DORSALLYconvergence:the tips will come togetherNeural plates starts "zipping" up/down atthe MIDBRAIN@ 19 days:- Open neural plate - Remaining primitive streak@ 20 days:Neural Plate forms in middle of embryo and then closes up as zipper going in both directions@ 22 days:neural tube opened at posteriorally end of embryo but closed at anterior end@ 23 days:Almost close only open at the endsNeural tube closure in chickis initiated at the level of the future midbrain and "zips up" in both directions.Caudal neuroporesare the last regions to close are the large openings at either end of the neural tubeNeural Tube Closure Defects- occur in the most cranial and caudal regions because they are the last to close - are caused when various part of the neural tube fail to close. **are among the most common congenital anomalies**Failure to close the neural tubeoccurs most frequently in the cranial and the caudal regions.AnencephalyFailure to close the anterior neural tube regions. (forebrain remains in contact with the amniotic fluid and degenerates)Spina BifidaFailure to close the neural tube in the caudal region -The severity of which depends on how much of the spinal cord remains exposed. -The most severe cases of spina bifida involve protrusion of the spinal cord and meninges through the defective vertebral arches and other superficial structures (spina bifida cystica).Craniorachischisisopen brain and spinal cordNEURAL CREST DEVELOPMENT-developed from neural plate -> tube formation - neural crests will lose contact and migrate to the developing embryo -Neural plate thickens folds -Narrow band of cells between the 2 cell types epithelium to mesenchymal transitional lose connection from neighboring cells become mesenchyme -Neural crest cells have spontaneous ability to move above from epidermis and go from epithelium to mesenchymal transition * Can migrate quite a distance -Migratory behavior is associated with changes in cell adhesion properties. -To migrate neural crest cells will undergo a process known as -epithelial-to-mesenchymal transition (EMT).NEURAL CRESTstem cell like population, give rise to a broad array of derivativesNeural crests providesprovides innervation to the entire digestive systemCranial neural crest(derived from the hindbrain) migrate dorsolaterally and contribute to the craniofacial mesenchyme that differentiates into cartilage, bone, cranial ganglia (neurons and glia) and connective tissues of the facePharyngeal archesorigin of craniofacial skeletal elements derived from the neural crestCardiac neural crestcan give rise to the entire musculo-connective tissue of the large arteries as they arise from the heart and to the septum which separates the pulmonary artery from the aorta. -septum of the outflow tract of the heart & wall of large arteries -first somite to fourth somiteVagal neural crest-Parasympathetic enteric ganglia of the gut -First somite to seventh somiteTrunk neural crest-Melanocytes, dorsal root ganglia, sympathetic ganglia & adrenal medullaSacral neural crest-parasympathetic enteric ganglia of the gut -the most distal portion of the neural crestDEFECTS OF NEURAL CRESTdoesn't migrate to proper location/doesn't differentiate correctlyNeurocristopathies-Group of diseases associated with abnormal development of the neural crest. -Result of defects in neural crest cells themselves but also of defects in the environment through which they migrate. -Defects affect only a single derivative of the neural crest, whereas other defects result in a wide array clinical manifestations.Hirschprung's Disease-Rare congenital disease 1:5000 live births -Mutations in Sox10 and Endothelin Receptor B -Aganglionic megacolon (absence of enteric neurons in the colon) -Often associated with pigmentation defects and deafnessTreacher Collins Syndrome / Mandibulofacial Dysostosis-Autosomal dominant craniofacial disorder (1:50,000 live birth) -Mutations in the TCOF1 gene, which encodes the nucleolar protein Treacle1 -Minimum number of cell death --> excessive cell death (deficiencies in number of neural crest present in early embryo)Madibulofacial dysostosis Diagnosis1st and 2nd branchial arch syndrome (Treacher Collins Syndrome) Clinical diagnosis: - Hypoplasia of facial bones (mandibule and zygomatic complex) - Downward slanting of palpebral fissures - Defective middle ear ossicles (hearing loss) - Alterations of outer ear shape and position - Dental malocclusion - Abnormal spacing and reduced number of teeth25 days-Pharyngeal pouches to which the neural crest cells will migrate28 daysEctoderm contribute to sense organsSense Organs• The sensory organs (epithelium of the nose, lens of the eye and inner ear) originate from thickening of the ectoderm in the head region, known as cranial placodes.cranial placodes> are induced by surrounding tissues > are thickenings of the cephalic embryonic ectoderm (thickened ectoderm at the anterior end of the embryo) Contribute to: + PITUITARY GLAND!!! / ADENOHYPOPHYSEAL GLAND + Cranial gangliaAdenohypophysis- anterior lobe of the pituitary gland - thickening of stomodeum (roof of mouth) - oral ectoderm invaginates to form RATHKE's pouch to form *ADENOHYPOPHYSES* - while the floor of the diencephalon invaginates to form the INFUNDIBULUM to form the "NEUROHYPOPHYSIS"Lens placodegive rise to lens (vision) >Diencephalon--> come in contact with ectoderm--> Induce thickening of ectoderm to give rise of to lens (optic cup give rise to retina)Otic placodegive rise to inner ear (hearing and balance) >Hindbrain region thicken --> invaginate to form otic pit --> put will eventually segregate to form otic vesicle --> semicircular canal (all components of inner ear)otic epitheliainduce chondrogenesis in the surrounding mesenchyme providing a protective and structural framework to inner ear.Olfactory placode- epithelium of nose (smell) - is required for normal forebrain development.Reciprocal interactions:-The lens is essential for the normal development of the adjacent structures, the retina, iris and overlying cornea. *Tissues neutrally induced will signal back to tissues inducing them --> determine their fate *required for normal brain developmentDelaminationSplitting or migration of one sheet into two sheets a. Trigeminal (ganglion CV V > ophthalmic : ophthalmic lobe of trigeminal > maxilomandibular: maxilomandibular lobe of trigeminal b. Epibranchial > geniculate: (dital ganglion CN VII > petrosal: distal ganglion CN IX > nodose: distal ganglion CN Xinvaginationthe folding in of a membrane or layer of tissue so that an outer surface becomes an inner surface > adenohypophyseal > lens > otic > olfactoryMesoderm DerivativesMesoderm is sandwiched between the ectoderm and the endoderm. our focus: -Notochord -Head muscle -Axial & limb skeleton -Axial & limb muscles -Body wall -Connective tissue of the skin future lectures: -Circulatory System -Heart -Kidneys -Ovaries -TestesMesoderm RegionalizationDuring gastrulation specific regions of the epiblast migrate through different regions of the primitive streak to form the mesoderm = FATE MAPPINGFate mappinganalyses indicate that mesodermal tissue regionalization depends on the position and the timing of cell passage through the node and the primitive streak in an anterior to posterior direction.No problem I love Embryon - notochord pm - paraxial mesoderm im - intermediate mesoderm lpm - lateral plate mesoderm eem - extraembryonic mesodermDevelopment of Mesoderm happensAnterior to posteriorSubdivisions of the mesoderm at the end of neurulation1-Chordamesoderm (axial mesoderm) -Notochord 2-Paraxial mesoderm -Head mesenchyme -Somites (i) Sclerotome (cartilage, bones) (ii) Myotome (skeletal muscle) (iii) Dermatome (dermis) (iv) Syndetome (tendons) Suck My D**** Science 3-Intermediate mesoderm -Kidney -Gonads 4-Lateral plate mesoderm -Splanchnic (visceral) mesoderm (circulatory system) -Somatic (parietal) mesoderm (body wall)Development of the mesoderm layer- After gastrulation we have three layer --> neurulation --> different regions of mesoderm start to segregate - Two layers of mesoderm: PARIETAL AND VISCERAL LAYERDerivative of the Notocord- The notochord will become the nucleus pulposus (chondrocyte-like cells). - It is later surrounded by the circular fibers of the annulus fibrosus. - Combined, these two structures form the intervertebral discDerivatives of the Lateral Plate MesodermDorsal, ventral, coelom, somatopleure, and splanchnopleureDORSAL component formsSOMATIC (parietal) MESODERM: o Body wall, lining the outside of the peritoneal, pleural & pericardial cavities o Mesodermal components of the limbs (except muscles)VENTRAL component formsSPLANCHNIC (visceral) MESODERM: o Covering of the abdominal organs, lung and heart o Circulatory system (heart, blood and blood vessels) o Muscle & connective tissue of digestive and respiratory tractsCOELOMspace between the 2 layers will form the BODY CAVITY o Abdominal region --> peritoneal cavity o Thoracic region --> pericardial & pleural cavitySomatopleureSomatic (parietal) mesoderm + ectoderm o Forms the ventral and lateral body wall. o Forms the membranes that line the peritoneal, pleural & pericardial cavities.SplanchnopleureSplanchnic (visceral) mesoderm + endoderm o Form the wall of the gut and the thin serous membrane around each organ.Embryo grows --> lateral flexion --> fusion of the two lateral plate mesoderm --> fuse at lateral end to SEGREGATE THE GUTo Visceral mesoderm associated with endoderm o Parietal endoderm associated with ectodermIntermediate mesoderm [lateral to the somite] gives rise toUrogenital system (their development is interconnected anatomically)Urinary Systemo Mesonephros and mesonephric duct (embryonic kidney) o Metanephros and metanephric duct (adult kidney)Genital Systemo Gonads(Testis/Ovary) o Genital tractsSomiteblocks of mesoderm that are located on either side of the neural tube in the developing vertebrate embryoSomite Development (paraxial mesoderm)- On each side of the neural tube, appears in the anterior region first --> and move to unsegmented region ( form in anterior --> posterior pattern) - Paraxial mesoderm cells become loosely organized into aggregation of cells called somitomeres. - The somitomeres eventually separate from the presomitic paraxial mesoderm to form individual somites. - Somites appear first in the anterior portion of the trunk, and new somites "bud off" form the unsegmented presomitic (PSM) at regular intervals.SomitomeresParaxial mesoderm cells become loosely organized into aggregation of cellsSomite Periodicity- Somites appear with a specific periodicity. - The periodicity is a highly regulated process (species specific) which depends on a segmentation clock established by the cyclic expression of genes of the **Notch** and **Wnt** signaling pathways. - The number of somites is usually a good indicator of the age of an embryo.Somite Differentiation- When the somite is first separated from the presomitic mesoderm, cells are not committed to a specific lineage. - As the somite matures, its various regions become progessively restricted to form only certain cell types.Somite Components(1) SCLEROTOME (cartilage, bones) > Ventral portion of somite --> delaminates & gives rise to structures all around the spinal cord > Primaxial dermamyotome: gives rise to muscles in the back (close to neural tube) > Abaxial dermamyotome: farthest form the neural tube (2) MYOTOME (skeletal muscle) (3) DERMATOME (dermis) (4) SYNDENTOME (tendons) >the last somatic compartment to form. >It forms at the boundary between the sclerotome and the myotome. >The syndetome give rise to tendon progenitors.What determine cell fate within the somite?A: Location, location, location! B. Tissues secretionAxial Skeletonskull, vertebral column, rib cageSkull developmentThe skull has a dual embryonic origin paraxial mesoderm (posterior) and neural crest (anterior)Vertebral column- Vertebrae are derived from the sclerotome portions of the somites - The sclerotome portion of each somite undergoes a process known as resegmentation - Each vertebra is formed from the fusion of the caudal half of one somite and the cranial half of its neighborLimb developmentOutgrowth of the embryonic body wall, consisting of mesenchyme derived from the somites and the lateral plate mesoderm. These precursors accumulate and proliferate under the epidermis to create: limb budLimb bud *The mesenchyme of the limb bud is derived from the mesoderm: somites (muscle precursors) and somatic lateral plate (skeletal precursors)Apical ectodermal ridge (AER)an important organizing center in the limb budProgress zone (PZ)Zone immediately adjacent to the AER Interaction between the AER and the PZ is critical to limb development > participate in the establishment of the proximal-distal axis of the limbProximal-distal axis of the limb- During outgrowth of the limb, cells of the PZ are assigned progressively more distal positional identities. - Cells leaving the PZ differentiate and their positional value will depend on the time at which they leave the progress zone. - The first cells leaving the PZ form proximal structures, the cells that have undergone numerous divisions in the PZ become the more distal structures. - As the bud grows cells leave the PZ and start to differentiate and cartilaginous structures begin to appear in the mesenchyme. - The part of the limb nearest to the body wall is the first to differentiate, and differentiation proceeds distally as the limb extends.Phocomelia- Thalidomide (sedative) prescribed in the 60's causes severe limb deformities if taken at critical times during pregnancy. - The long bones are shorter than normal and the more proximal elements are lost.ZPA- The anterior-posterior axis is specified by the posterior mesoderm of the limb bud known as the zone of polarizing activity (ZPA). - The pattern of digit formation is dependent upon the activity of the ZPA. > ZPA produces retinoid acid and sonic hedgehogAnterior transplantation of ZPAinduces duplication of the digits = polydactylyPolydactylyFormation of supernumerary digits hand is like a mirror of itselfCell death plays a major role insculpting the limb - It is essential for joints formation and for the separation of the digits.Apoptosisgenetically programmed cell deathSyndactylyAbnormal persistence of soft tissues between the digitsEndoderm DerivativesENDODERM: deepest germ layer o Digestive tract o Respiratory tract o Tonsils o Thyroid o Parathyroid glands o Thymus o Liver o Pancreas o Gall bladderGut and associated organ development- ENDODERM: forms lining/epithelia and secretory elements of the digestive tube and glands. - MESODERM: (mesenchyme) surrounds the tube and forms connective tissue and smooth muscles for peristalsis. > Gut associated organs are generated through reciprocal inductive interaction of endoderm and mesoderm (surrounding mesenchyme)Gut associated organs are generated throughreciprocal inductive interaction of endoderm and mesoderm (surrounding mesenchyme)Gut Formation- Lateral flexion: lateral plate flexes laterally & fuses to give the splanchnic & somatopleura - Longitudinal flexion: bending of the embryo in the anterior and posterior end --> individualizes the gut from the yolk sacGut Tube Regions (subdivisons)- Pharyngeal gut - Foregut - Migdut - HindgutGut Tube RegionalizationPlease Feed My HungerPharyngeal gutextends from the buccopharyngeal membrane to the respiratory diverticulum (pharyngeal pouches)Foregutextends to the liver bud (esophagus, stomach, proximal half of the duodenum, liver and pancreas) >>a ll glands associated with digestive tractMidgutextends to the proximal part of the transverse colon (distal half of duodenum, jejunum, ileum, cecum, and part of colon)Hindgutextends to the cloacal membrane (bladder, urethra, and prostate gland, the rest of the colon and rectum)Activation of transcription factorsis important in differentiation of gut > activation & specialization of gut is done by activating different regions of transcription factorsRegionalization of Gut Tube- Regional specification of the gut tube is initiated by a concentration gradient of retinoic acid. This gradient causes the expression of transcription factors in the gut endoderm that will determine the identity of the different gut regions. - The identity of the different gut regions is maintained through interactions between the gut endoderm and the surrounding splanchnic mesoderm. - Endoderm secretes SHH (sonic hedgehog) which differentially regulates HOX genes expression in the mesenchyme. >> Induces the dominant expression of HOX GENES --> providing POSITIONING IDENTITY along anterior-posterior axis - Different concentration of sonic-hedghog --> activates different concentration of HOX genesPhysiological Gut Herniation- Intestinal loops (midgut) enter the extraembryonic cavity in the umbilical cord during the 6th week. > RETRACTION is a natural process in which there is an enlargement of the umbilical cord as the gut loop is moving into the UMBILICAL CORD - Retraction of the intestinal loops is initiated during the 10th week and completed by 12th week.Development of the Respiratory System(1) The respiratory diverticulum (lung bud) appears around the 4th week. (2) Outgrowth from the ventral wall of the foregut. (3) The appearance and location of the lung bud are dependent upon an increase in retinoic acid produced by adjacent mesoderm. (4) Epithelium of the internal lining of the larynx, trachea, and bronchi, as well as that of the lungs, is entirely of endodermal origin. (5) The cartilaginous, muscular, and connective tissue components of the trachea and lungs are derived from splanchnic mesoderm surrounding the foregut. (6)Start with pharyngolaryngeal tube --> divides --> EVERYTHING FORM SPLANCHNIC MESODERM EXCEPT BUDStages of Pulmonary Development (pneumonic: every person can suck air)EMBRYONIC @ week 3-7 - lung bud formation - trachea and bronchi differentiate PSEUDOGLANDULAR @ week 5-17 - branching of the conducting airways up to the terminal bronchioles CANALICULAR @ week 16-16 - terminal bronchioles divide into respiratory bronchioles - terminal bronchioles divide into alveolar ducts - appearance oh Type-I-pneumocytes SACCULAR @ week 26-36 - terminal alveolar - surfactant detectable ALVEOLAR @ week 36-3 years - alveoli maturation - well-developed alveoli capillary interfaceStages of Pulmonary Development remember byEvery Person Can Suck AirBronchiole tree developmentCONDUCTING PORTION [trachea > bronchi > bronchioles > terminal bronchioles] > RESPIRATORY PORTION [respiratory bronchioles > alveolar ducts > alveolar sacs]Most organs already in place by8th week, anything happening after that is DEVELOPEMENT & GROWTHFetal period characterized by:o maturation of tissues and organs o rapid growth of the body (length and weight) o growth of the head slows downRatio of head to bodyo 3rd month: head is 1⁄2 of the size of fetus o 5th month: head is 1/3 size of fetus o birth: head is 1⁄4 size of fetus11-week Human Fetus- 5-7 cm (crown-rump length = top of head to bottom) - Swelling of the umbilical cord --> because of physiological herniation taking place - Digits are well developed - Irregular skull contours - Eyes ventrally located --> eyes were originally more dorsal position & moved12-week Human Fetus- ~ 8 cm (crown-rump length) - Primary ossification centers formed - External genitalia recognizable - Vascularization visible - Retraction of herniated loops - Muscular activity18-week Human Fetus- ~ 15 cm (crown-rump length) - Eyebrows and head hair visible - Outer ears in their final position28-week Human Fetus- ~ 27 cm (crown-rump length) - Well-rounded contours - Most organ systems are functional - Except respiratory and nervous systems - Birth at 7 months = 90% survival chanceThe placenta is theprimary site of nutrient and gas exchangePlacenta is afetomaternal organ that has 2 components: - fetal component (chorion) - Maternal componentFetal component (chorion)derived from the trophoblast and extraembryonic mesodermMaternal componentderived from the uterine endometriumFunction of the Placentao Protection o Nutrition o Respiration o Excretion o Hormone productionAs the fetus grow there is a(n):increase in nutrients demand to provide to growing organs > demand is meet by an increase in surface area between maternal and fetal components. Via development of: CHORIONIC VILIVilli are formingaround ENTIRE REGION OF CHORIONChorionic Viliincrease surface area (SA) between maternal + fetal component = facilitates exchange of nutrients/wasteFORMATION OF THE VILLUS- Embryo is anchored into the endometrium of the mother - The trophoblast = multinucleated tissue with no membrane to separatePRIMARY VILLUScytotrophblast & synchtrophoblastSECONDARY VILLUSwhen the extrembryonic mesoderm invaginates between the syncytophoplast > mesoderm coreTERTIARY VILLUSo Blood vessel form o Lacunae are forming (vacuoles) in which the mothers blood is dumping > remember blood vesselsRELATION OF FETAL MEMBRANES TO WALL OF THE UTERUS (2nd - 3rd month)- Decidua parietalis --> fuses with decidua basalis - Decidua capsularis --> degenerates - Decidual basalis (from mother) + chorion frondosum (from embryo) --> eventually form the placenta - Chorion frondosum --> region where chorion REMAINS (because embryo attached) - Chorion laeve --> chorion is GONE (embryo DID not attach)Birth defectcongenital malformation = congenital anomaly > structural, behavioral, functional, and metabolic disorders present at birth.Birth defects arethe leading cause of infant mortalityMajor anomaliesoccur in ~3% of live-born infants.Minor anomaliesoccur in ~15% of newborns.Genetic factorsaccount for approximately 28% of birth defectsEnvironmental factorsproduce approximately 3% to 4%of birth defects.Multifactorial inheritanceproduces 20% to 25% of birth defectsIn 40% to 45% of birth defectsthe cause is unknown. >> CRITICAL PERIOD SO THAT EVERYTHING IS HAPPENING RIGHT TO PREVENT RISK OF MALFORMATION LATERTYPES OF ABNORMALITIES- Disruptions - Deformations - SyndromesDisruptionsmorphological alterations of already formed structuresDeformationsresults from mechanical forces that mold a part of the fetus.Syndromeso A group of anomalies occurring together that have a common cause. o Multiple manifestions & pigmentsEnvironmental Factors- Infectious agents - Radiation - Chemical agents - Nutritional deficiencies - Maternal disease(1941) German measlesthat affected a mother during early pregnancy caused abnormalities (cataract & heart defects) in the embryo.(1961) thalidomide- First report linking limb defects to a sedative thalidomide - Evidence that drugs could also cross the placenta and produce birth defects --> absence of the long arms so that head is attached to shoulder = PHOCOMELIAPHOCOMELIAhead attached to shoulderThe structures more sensitive to others to birth defectBy study done in (2010) by CDC + National Birth Defects Prevention Network 1st common: CLEFT PALATE & CLEFT LIP! 2nd common: CARDIOVASCULAR SYSTEM DEFECTS --> tetralogy of Fallot 3rd common: GI TRACT DEFECTS (neural crest defects) 4th common: CHROMOSOMAL MUTATIONS ( trisomy 21) --> turners syndrome: (X0) patient is female but lacks one of the 2 X chromosomes, fertilityPrenatal diagnosisultrasound, maternal serum screening, amniocentesis, chorionic villus samplingULTRASONOGRAPHYo Noninvasive technique that uses high-frequency sound waves reflected from tissues to create images. o Transabdominal or transvaginal (higher image resolution) o Performed between 18 & 20 weeks o Assess overall growth & development, and birth defectsMATERNAL SERUM SCREENINGo Concentrations of serum a-fetoprotein (AFP). o AFP is produced normally by the fetal liver --> peaks at approximately 14 weeks, and pass into the maternal circulation via the placenta. o AFP concentrations increase in maternal serum during the second trimester and then begin a steady decline after 30 weeks of gestation. o Test is performed between 15 & 20 weeks of gestation. o AFP can be used in combination with other markers such as unconjugated estriol (uE3), human chorionic gonadotropin (hCG) and inhibin A.Increased AFPNEURAL CREST DEFECTDecreased AFPCHROMOSOMAL ABNORMALITYAMNIOCENTESIS[not enough cells, very long process] o Approximately 20 to 30 ml of fluid is withdrawn from the amniotic cavity. o Procedure is performed transabdominally, in the second trimester (15 & 20 weeks). o The fluid is analyzed for biochemical factors, such as AFP. o Fetal cells are recovered in the amniotic fluid --> a. Perform karyotyping (several weeks) OR b. Polymerase chain reaction can be performed to test for specific genetic diseases.CHORIONIC VILLUS SAMPLING[can be performed earlier] o Collection of approximately 5 to 30 mg of villus tissue. o Performed in a transabdominal or transcervical manner (between 10 & 12 weeks). o Detection of genetic disorders and chromosomal anomalies (results in few days). o Disadvantage: This method does not assess neural tube defects or other malformations. o Advantage: have sufficient amount of cells in culture & can detect disease in a few days (FASTER) vs. amnio where you cant get enough cells & it takes LONGER