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138 Lectures 15-18 and Wk10 OH's
Terms in this set (55)
What structures start as placodes? What is a placode?
Sensory organs and cutaneous structures
A placode is a thickened area of the ectoderm.
Where does the sensory pre-placode form?
Anterior region of the medium BMP ectoderm (boundary of epidermis and neural plate)
What forms from the non-anteriorest part of the medium BMP ectoderm?
Neural crest cells
Pax6 - definition and function
Homeobox-containing transcription factor, induces most anterior sensory structures: nasal and lens
Why is the lens sensory placode special?
It does NOT form neurons
What structures are involved in formation of the lens, and how do they and lens form?
Optic vesicle: outgrowth of brain, induces lens placode in surface ectoderm
Lens placode then induces optic vesicle to become the optic cup
Where is Pax6 expression high?
In areas with both low BMP and low Shh
What happens with Pax6 KO/Over expression?
KO: no eyes, messed up face
What happens to the face during an Shh knockout? Why?
Cyclopeia (holoprosencephaly) - 1 eye, no formation of separate brain hemispheres due to expanded region of Pax6 activity
What happens to the face during an Shh over expresion? Why?
No eyes, due to reduced Pax6 activity
What are the ectodermal appendages?
hair, nails, feathers, sweat/mammary glands - the cutaneous structures
How are the ectodermal appendages formed?
Reciprocal interactions between the epithelium and underlying mesoderm
What germ layer decides what cutaneous structures form? How is this shown (specificity types)?
Regional specificity - explants of epithelial placodes and underlying mesoderm from other regions=gain mesoderm's normal structure
Genetic specificity - mesoderm from other animals won't induce the other animal's structure jesus christ obviously
Forming Cutaneous structures - the steps
1) Signals between ectodermal epithelium and underlying mesenchyme make epithelial placodes (don't mix up with sensory placodes or josh will make fun of you in office hours)
2) Reciprocal signaling condenses mesoderm under placode
3) More reciprocal signaling leads to continuing development of cutaneous structures
What is ectodermal dysplasia and why does it suck to have?
Less/messed up cutaneous structures development
Caused by mutations in Eda-R (in epith placode) and Eda (signal produced by surrounding ectoderm)
How does Eda-R signaling work?
Forms a +-feedback loop with Wnt signaling, which is high in the placodes
How are endoderm and mesoderm induced in birds/mammals?
They are the ones that ingress through the primitive streak (no idea how endoderm is specified separately from mesoderm, it's just the bottom part)
How is left-right asymmetry of the endoderm established?
Node cell cilia beat in the same direction (this is easily the weirdest mechanism yet)
Cilia mutations (eg in dynein) cause randomization of organ locations
Why does this class discuss so many fucκed up genetic disorders?
Dr. Lyons feeds on our horror
How does the endoderm get patterned?
Mesoderm! It expresses TF's that create endoderm regions (fore, mid, hind)
Boundaries of TF expression are morphological boundaries
What does Cdx2 loss cause?
Loss of Cdx2 puts intestinal cells in stomach
What mesodermal signals allow it to pattern the endoderm?
Hox gene expression in mesoderm - corresponds with endoderm region boundary
Why are endodermal patterning and cutaneous structure patterning similar
Both change structures if co-cultured with mesoderm of a different area, to match the area the mesoderm would normally induce
What cell movements are involved in branching morphogenesis?
invaginating, apical constriction, ingression, etc
What genes and structures control branching morphogenesis (use example)?
Mesodermal Hox genes induce mesoderm to secrete FGF10 to cause lung BM
KO FGF10 = no lung forms
What are villi and how do they self-renew?
They're folds in the intestines that have a crypt at their base with stem cells to replace their dying bits
How are the SC's in the crypt maintained?
crypt-adjacent mesenchyme secretes BMP inhibitors/Wnt signaling, inducing hella B-catenin to maintain stem cell population
The mesenchyme around the villi themselves make BMP's which induce differentiation
What stabilizes B-catenin in cells?
TCF/LEF, lets it get into the nucleus
How does B-catenin maintain stem cells as stem cells?
Induces EphB, while the villi make ephrin = REPULSED AF
APC does what
Degrades B-catenin, lose it = booty cancer
What germ layer types is a limb bud made of?
Surface ectoderm and mesoderm
What parts of limbs come from mesoderm?
What direction does the limb develop
Proximal to distal
How do limb digits separate?
Apoptosis of the surrounding cells
What are the two limb bud signaling centers?
Apical ectodermal ridge (AER) and the Polarizing region (PR)
What does AER loss induce? Name of associated disease?
Increased progress zone apoptosis and decreased differentiation, humans get Split Hand/Foot Syndrome
What signaling molecules does the AER make?
FGFs 4 and 8
How does limb bud prox/dist axis identification occur? Experiments to support this?
Hypothesis: length of time in PZ/length of time under AER signal, perhaps due to chromatin changes?
Transplant young PZ and AER to old limb bud or vice versa: transplanted PZ grows according to age irrespective of where it's transplanted
Transporting AER alone onto old/new PZ does not affect PZ differentiation
Thalidomide - why was it a bad idea?
Give for morning sickness (good job, europe) but causes shortened, distalized limbs - possibly prevents differentiation from PZ so limbs shorten and all are induced with distal signals
What genes are known to pattern full limb Prox/Dist axis?
Hox genes, KO Hox genes causes specific limb structure loss (Also help pattern A/P axis)
Polarizing Region - what axis does it signal? What signal does it secrete?
A/P (it does posterior), secretes Shh
How do the limb bud areas specify each other?
PR - Shh maintains PZ and FGF expression in AER
AER - FGF8 maintains PZ and PR
PZ - Secretes FGF10 to maintain FGF8 expression in AER (+ feedback) - No FGF10 means no limb dev
What happens if you replace the PR with flanking mesoderm (nonsignaling)?
The AER degenerates, therefore PR is necessary to maintain AER
How do Hox genes effect the limb A/P axis?
Different Hox genes induce the expression of TF's in the lateral plate mesoderm, eg Tbx4 and 5 in hindlimb/forelimb respectively both activate FGF10
Limb-specific Shh enhancer - what do mutations in it cause?
Shh enhancer defects serpentize animals (like snakes normally) - induces serpentized mouse
Overactive Shh enhancer - too many digits
How can maternal determinants be localized?
Either by transcript position (bcd/nanos) or by activity restrictions (Toll-R, DORSAL)
What happens to an enucleated, fertilized MAMMAL egg?
It does not develop at all because mammals have no maternal determinants that can support early cleavage alone
Are Wg and Hh morphogens in flies?
YES - induce gradients at A/P ends
From which part of the ectoderm does the cutaneous structure pre-placodal region originate?
Everywhere EXCEPT areas where NCC's form - middle levels of BMP (middle of D/V axis), mid to high Wnt (all but most anterior end of A/P axis)
All Shh roles (4)
1. Ventralize the neural tube
2. Induce sclerotome formation from somites (instead of dermatome)
3. Regulates sensory placode development via Pax6
3. Posterizes limb buds (and maintains distalizing AER)
What does FGF8 do? (3)
1. Clock-wavefront for somite differentiation
2. Induce A/P axis of fore and midbrain
3. AER signal to PZ in limb development
What does FGF10 do? (2)
1. Signals lung endoderm to undergo branching morphogenesis
2. PZ signal to AER in limb development
+ feedback examples covered?
Wg/Hh, FGF8 and 10/FGF8 and Shh in limb development
What part of asymmetric neuronal divisions in the VZ specify a cell as a neuroblast?
If it doesn't retain its APICAL process, it's gonna move and develop
What is "point to point correspondence?"
How each photoreceptor from the retina makes its way perfectly to the correct part of the tectum
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