quiz 4 Flashcards
gastrulation
early formation of different germ layers
blastocyst
inner mast cell - develops into outer layer (tropoblast and embryo) - becomes placenta in mammals
totipotent vs pluripotent
totipotent - can create a complete organism (placenta included)
pluripotent- cant
epigenetics
how a cell remembers what it should become based off of changes of structure of genome that permits certain genes to be opened or closed
1. combination control
2. cell memory
morphogen
long-range inductive signalling that exert graded effects (varies by conc)
AV axis
animal vegetal
-internal vs external
AP axis
anterior posterior
-head vs tail
DV axis
dorsal ventral
-back vs belly
when is AP axis determined
prior to fertilization (due to bicoid)
bicoid- how does it give rise to AP axis
at anterior pole, diffusion gradient away from point gives rise to AP axis
mechanisms of pattern formation- AP axis
-bicoid
-gap genes
-pair-rule
-segmental polarity
bicoid role, regulation and what happens if mutated
-gives head and tail (AP)
-prior to cellurization
If mut: lose segmentation
gap gene role, regulation and what happens if mutated
-subdivides core segments
-active when bipoid is low
If mut: gets head, tail and only one area in between
pair-rule role, regulation and what happens if mutated
-divides ares defined by GAP
(1/2 of each segment under influence of pair-rule)
-gap genes drive expression of pair role (co-exressed with Gap)
If mut: no segmentation of segments
segmental polarity genes (ie. Hedgehog) role, regulation and what happens if mutated
-gives polarity to each segment, so that 1/2 of each segment is not a mirror image of whats next to it
-pair-rule (?) further divides segments, drives segment polarity genes
If mut: all segments are the same
what do segmental genes do
control drosophila segmentation along AP
subdividing of drosophila embryo
-one cell makes and secretes wnt, -acts on neighbouring cell thru effector protein (engrailed)
-engrailed signals for synthesis and release of hedgehog
- hedgehog further promotes release of WNT
-after 3 dcell divisions along AP engrailed is stabalized and no longer needs WNT
hox
locks in and stabalizes patterning
what is hox controlled by and what 2 complexes does it function thru
WNT and HH
Bithorax complex (abdominal and thoracic)
Antennapedia complex ( thoracic and head)
loss of hox
cells that are all alike, can develop segments at wrong place
sequential gene activation
posterior genes inhibit anterior
-if most posterior gene is on, no other ones are
-changes in chromatin structure and sequential opening/closing of heterochromatin
trithorax
keep chromatin open once hox genes are on (most posterior gene dominant)
polycomb
keep chromatin closed in regions where hox is not expressed
mutation is esc gene
blocks polycomb, all chromatin pen and all hox genes on
nodal
TGFR activator, acts locally (diffuses slowly)
-more nodal active @ vegetal pole (V) becomes endoderm
lefty
SMAD inhibitor, acts distal to site of secretion (diffuses rapidly)
-more lefty active @ animal pole (A) becomes ectoderm
high BMP
epidermal tissue (ventral)
low BMP
neural tissue (dorsal)
noggin and chordin
TGF antagonist - SMAD inhibition
block BMP on dorsal side (not ventral) in gradient manner
active notch
stay projenitor
inactive notch
differentiate
stem cell
-can divide indefinitely,
-makes multiple cell types
-exists for entire life of the organism
progenitor cell
-divide a finite number of times
-have already specialized to make restricted cell type
embryonic stem cell
does not qualify by standard definition of stem cell - only exists for a short period of time
neural tissue comes from
ectoderm
neural cell formation
ectoderm –> neuroectoderm –> neural tube –> neural cells
signals needed for neural cell form
-cytoskeletal remodelling
-morphogens - receptor signalling
-chemoattractants/ repellants
bending of epi cells facilitated by
actin/myosin contraction - mediated by Rho-GTPases
notochord
releases many morphogens
-cells proliferate and migrate inwards –> differentiates based on proximity to notochord
RhoA staining experiment
RhoA clusters toward surface of folds - acts on adhsion belt to cause contraction -invagination - closing of tube
ROCK inhibitor
no contraction of actin adhesion belt = no invagination of neural tube
2 WNT signaling pathways
canonical: B-catenin transcriptional co-activation
- generation of neural progenitors and specialized sub-types
non-canonical: dishevelled activates Rho/ROCK and alters cytoskeleton
-neural tube closure and cytoskeletal dynamics
shRNA
gene silencing effect
shRNA against frizzled
inhibition of Wnt
morphogen spinal cord example
epi wall of neural tube thick –> forms small central channel
-different neurons form along DV axis
Motor neuron - ventral side
Sensory neuron - dorsal side
Shh released from
floor plate (notochord), diffuses up
BMP/Wnt released from
roof plate, diffuses down
high WNT/BMP low Shh
sensory (dorsal)
high Shh low WNT/BMP
motor (ventral)
pax
divides neural projenitor cells into broad dorsal-ventral domains
BMP what Pax
dorsal pax 3 and 7
inhibits ventral pax 6
Shh what pax
ventral pax 6
pax 6
activates neuronal (ectodermal) genes while repressing endodermal and mesodermal
spinal cord further subdivided by expression of
basic helix-loop-helix (bHLH)
homeodomain (TFs)
neural tube failure to close at top vs bottom
bottom - mild
top - no brain development, fatal
radial glial cells
-specialized neuroectoderm cells
-functions as stem cell - can give rise to neurons and glia
-forms scaffhold on which neurons can migrate
N-cam
neural cell adhesion molecule
-growth cone guidance thru cell surface adhesion
NG2
chrondroitin sulfate proteoglycans
-inhibits growth cone migration thru contact inhibition
commissural axons
travel from one side of body to another, coordinate movement
commissural neurons in spinal cord
-commissural neurons send axons ventrally to floor plate
-drawn by a Netrin gradient (chemotaxis)
-Netrin secreted by floor plate
-Netrin then turns at right ang;e
DSCAM
neighbours never express same DSCAM
-cadherins bind cadherins of same type
-in THIS case: binding = repulsion
-same DSCAM = repel
dendrites and axonal branches from the same neuron ________ eachother
avoid
autapses
self-synapse (axon syapses w own dendrite)
synaptic pruning
synapse elimination
endoderm tubes
- digestive - extend thru body; lover, pancreas, gallbladder
- respiratory - outgrowth of digestive tube; 2 lungs
endoderm function
construct lining of tubes
gives bulk of internal organs
pharynx
common chamber shared by tubes
-anterior region of embryo
-epithelial outpockets give rise to thyroid, tonsils, thymus, and parathyroid glands
pharynx and pharyngeal pouches
within developing embryo:
-tubes w folds develop into organs
-fore, mid, hind gut
-pocket and offshoot develop: depends on position (how much Gf they are exposed to)
purpose of crypts
1). constant/quick proliferation: protect lining from mutations
2). control signaling
absorptive cell
dense layer of microvilli
-take in nutrients from lumen
goblet cell
secrete protective coat of mucous
-secrete mucous into lumen
paneth cell
gut immune response against bacteria
-secrete signal factors into lumen
enteroendocrine cell
secrete hormones that help control appetite satiety and cell growth
-secrete hormones into blood - signal if there are nutrients present or not
BrdU labelling is incorporated during _____ phase
S
APC mutation
loss of scaffhold or gsk3b complex
-cant degrade beta catenin
wnt secreted by
paneth cells
what maintains notch expression
Wnt
active Notch in presence of Wnt
cells proliferate and specify to transit amplifying cells
block wnt
cells lose notch ; differentiate to absorptive cells
active delta no wnt
differentiate to goblet/ secretory cells
notch expression in crypt cells
expressed in all cells in crypt
what cells express delta and what expresses notch
delta - paneth cells
notch - stem cells
delta
inhibits notch cell from differentiating, differentiates into secretoary cell
what if there was no notch
all cells in crypt would differentiate
epithelial vs mesenchymal
Epithelial:
-apical-basal polarity
-contact w basal basement membrane
-extensive cell-cell contacts
-E-cadherin
-cyto-keratins (ECM)
Mesenchymal:
-anterior-posterior polarity
-absence of cell-cell junctions
-N-cadherin
-mesenchymal specific vimentin (ECM and integrin binding)
WNT and TGFb to support EMT
TGFB - SMAD - drive expression of EMT-TFs (eg. snail)
WNT- Frizzled/b-catenin - activate EMT-Tfs thru GSK3b inhibition
INHIBITION OF GSK3B BLOCKS SNAIL DEGRADATION
snail
active in nucleus
-represses E-cadherin
-drives expression of N-cadherin and vimentin (switch to mesenchymal)
tumors and EMT
become more invasive and metastatic
tumors EMT process
normal epi layer undergos EMT
- cells migrate out
- if accumulated mutation, cancer cells migrate
when is DV axis defined
at the time of fertilization
neurons must be ensheathed by ________ to facilitate communication over long distances
support cells (oligodendrocytes)
chat gp
