[LE 02] Ectodermal Derivatives Flashcards
Neurulation, Neural Tube Development
ectoderm fates
- epidermal cells of the skin
- neuron of the brain
- pigment cell
mesoderm fates
- notochord
- bone tissue
- tubule of the kidney
- RBCs
- facial muscle
endoderm fates
- stomach cell
- thyroid cell
- lung cell
t or f: differential signaling contributes to specification of germ layer fates
t
in the specification of the germ layer fates, these are inhibitors in the early stage of the pathway that will induce endoderm formation
- wnt
- bmp
- activin
wnt, BMP, and activin inhibits
FGF
t or f: inhibition of FGF in the specification of the germ layers forms the endoderm
t
in the specification of the germ layer fates, what signal/s is/are found anteriorly?
activin and nodal
induces the formation of ectoderm cells
FGF
t or f: BMP4 induces the formation of neural cells
f; epidermal cells
t or f: high BMP4 induces the formation of posterior populations and the mesoderm in the germ layer fates
t
t or f: high activin/ nodal induces the formation of anterior populations in germ layer fates
t
t or f: presence of FGF in the specification of germ layer fates induces the formation of ectoderm cells
t
t or f: endoderm will undergo neurulation to form the neural tube
f; ectoderm
t or f: neurulation has one mechanism
f
different neurulation mechanisms
- primary neurulation
- secondary neurulation
- junctional neurulation
it is the intermediate step in neurulation
junctional neurulation
how is the neural tube formed in primary neurulation?
forms from neural folds
how is the neural tube formed during secondary neurulation?
it is formed from mesenchyme
it is the transition between the primary and secondary neurulation
junctional neurulation
t or f: dissociated cells of the ectoderm become epidermal cells
f; neural cells
t or f: dissociated ectoderm cells with BMPs become epidermal cells
t
t or f: intact ectodermal cells become epidermal cells
t
t or f: intact ectoderm cells become neural cells in the presence of BMP inhibitors
t
BMP inhibitors
- chordin
- noggin
- follistatin
t or f: presence of BMP inhibitors induce the formation of the epidermal cells
f; neural cells
t or f: neural tissue is specified prior to gastrulation by the primary organizer
t
t or f: absence of signals from the primary organizer supress neural differentiation
t
BMP inhibitors that induce neural cell formation is from what structure?
primary organizer
structure that acts as an inducer for neurulation
notochord
t or f: presence of BMP induces formation of epidermal cells
t
it induces the neural plate formation
notochord
it secretes the BMP inhibitors wo induce the formation of neural plate
notochord
steps of primary neurulation
- elongation and folding of neural plate
- bending of neural plate
- convergence of neural folds
- closure of neural tubes
t or f: BMP is present during neurulation
f; it is inhibited
the median hinge point can form different shapes because of
PCP pathway and apical constriction
t or f: there are cells that undergo MET during neural tube closure
f; EMT
transmembrane protein present in the Shh signaling pathway
PTCH and SMO
relationship between PTCH and SMO in the Shh pathway
PTCH inhibits SMO
steps if Shh pathway is inactive
- PTCH inhibits SMO
- SUFU sequesters GLI1
- there is no transcription
steps if Shh pathway is active
- Shh binds to PTCH
- SMO is active
- SMO inhibits SUFU
- GLI1 accumulates
- there is active transcription
result of the Shh pathway
- proliferation
- apoptosis suppression
- stem cell self-renewal
interplay between these signals establishes the dorsal-ventral axis of the neural tube
Shh and BMP
t or f: interplay between Shh and BMP establishes the anterior-posterior axis of the neural tube
f; dorsal-ventral axis
antagonism between these signals contributes to neural tube dorsal-ventral patterning
Shh and Wnt/ beta-catenin
t or f: Shh and wnt/ beta-catenin are protagonists during the neural tube dorsal-ventral patterning
f; antagonists
highest signal present in the ventral side of the neural tube
Shh
highest signal present in the dorsal side of the neural tube
Wnt/ beta-catenin
t or f: Shh increases from dorsal to ventral neural tube
f; decreases
signal that promotes dorsal identities of the neural tube
wnt/ beta-catenin
wnt expresses this signal to inhibit Shh in the dorsal side of the neural tube
Gli3
signal expressed by Shh in the ventral side of the neural tube
Gli1
t or f: Shh gradient across the dorsal-ventral axis determines neural cell fates
t
t or f: the activator form of Gli is promoted by wnt/ beta-catenin
f; shh
how does wnt/ beta-catenin restrict Shh activity on the dorsal side of the neural tube?
it induces Gli3 expression
t or f: the presence of Gli1 promotes ventral neural tube determination
t
t or f: presence of Gli3 promotes the ventral determination of the neural tube
f; dorsal
signal interactions which determine the location of the hinge points
Shh-noggin-BMP
t or f: BMP gradient across the dorsal-ventral axis determines the neural cell fates
f; Shh gradient
signal which inhibits hinge point formation
BMP
hinge points that do not form when BMP is present
median hinge point and dorsolateral hinge points
what happens if noggin is reduced during hinge point formation?
BMPs initiate wnt and activate EMT in the neural crest cells
t or f: low BMP = no hinge point formed
f; there is hinge point formed
it inhibits BMP during hinge point formation
noggin
t or f: there is hinge point formation when noggin is present
t
regulates the fusion of the neural folds
differential expression of cadherins
cadherin present in the presumptive epidermis
e-cad
cadherin present in the neural plate
n-cad
signal which specifies the neural crest cells
wnt
signal that is concentrated in the neural plate
FGF
signal that is concentrated in the neural crest
wnt
cell movement involved in the formation of the neural crest
delamination
gene expressed and activated by BMP and wnt for neural crest to undergo EMT
Snail2
signals activated for neural crest to undergo EMT
wnt genes
during EMT of neural crests, wnt genes are activated by
BMP
steps in neural crest EMT
- start with differential cadherins
- EMT via activation of wnt genes by BMP
- Pre-migratory NCs have high BMP and intermediate wnt
- increased snail2 and RhoA and Rac activation
role of snail2 in neural crest EMT
represses N-cad, E-cad, Sox2 to promote delamination
repression of these signals promotes delamination
- n-cad
- e-cad
- sox2
t or f: pre-migratory NCs must have low BMP and intermediate wnt
f; high BMP
where does secondary neurulation occur in mammals and birds?
caudal region
steps in primary neurulation
- initial epithelium
- columnarization
- rolling/ folding
- closure
- neural tube complete
steps in secondary neurulation
- dispersed mesenchyme
- mesenchymal condensation
- medullary cord/ neural rod
- epithelial transition/ cavitation
- neural tube complete
forms when the mesenchyme condenses during secondary neurulation
medullary cord/ neural rod
the mesenchyme during secondary neurulation undergo this process to form a rod
epithelial transition
secondary vesicles from the forebrain
telencephalon and diencephalon
secondary vesicle from the midbrain
mesencephalon
secondary vesicles from the hindbrain
metencephalon and myelencephalon
adult derivatives of the telencephalon
- olfactory lobes
- hippocampus
- cerebrum
adult derivatives of the diencephalon
- retina
- epithalamus
- thalamus
- hypothalamus
adult derivatives of the mesencephalon
midbrain
adult derivatives of the metencephalon
- cerebellum
- pons
adult derivative of the myelencephalon
medulla
anteriorizing signals in the neural plate stage
- cerberus
- dickkopf
- Tlc
posteriorizing signals in the neural plate stage
- wnt
- FGF
- RA
it is an anteriorizing signal that is secreted later the neural plate stage
Tlc
why is Tlc secreted later?
to specify the forebrain
t or f: signaling proteins that specify the different brain regions is time-dependent
t
first signals demarcating the isthmus
Otx2 and Gbx2
it acts as an organizing center to establish the midbrain and hindbrain
isthmus
secondary anterior signals in specifying the different brain regions
- wnt1
- en1
- pax2
secondary posterior signals in specifying the different brain regions
- fgf8
- en2
- pax2
these are signals that are eventually expressed in the midbrain and hindbrain
Pax 2, 5, 8
signals that demarcates the forebrain-midbrain
Pax6 vs. En1/Pax2
demarcates midbrain-hindbrain
Otx2 vs Gbx2
specifies the hindbrain and telencephalon
Fgf8
signal that stabilizes expression of En1 and Pax2
Fgf8
specifies the isthmus
Pea3
it is the anterior-posteriorizing organizing center of the brain
isthmus
signal that the “telencephalon” organizing center expresses
Fgf8
dorsal-ventral axes specifying signals of the brain
Shh vs BMP
signals secreted by the isthmus
- wnt1
- Fgf8
anterior signal secreted by the isthmus
Wnt1
posterior signal secreted by the isthmus
Fgf8
t or f: interactions between signals may also specify neuronal populations
t
birth defect that happens when a baby’s backbone does not form normally
spina bifida
it is the forebrain specifying organizing center
“telencephalon” organizing center
defect wherein the brain and spinal cord are completely open
craniorachischisis
defect wherein brain is open and there is no skull vault
anencephaly
defect wherein there is herniation of the meninges and brain
encephalocele
defect wherein there are occipital skull and spine defects with extreme retroflexion of the head
iniencephaly
what does the Cre-Loxp mutant mouse do?
allows for precise deletion of genes of interest
new way of knocking out of gene
use crespar
deletion of this protein results in encephalocele
Gpr161
role of Gpr161
Shh inhibitor
cre driver in encephalocele
wnt1
t or f: mechanisms involved in NTDs are likely to be multi-faceted
t
what happens when the neuroepithelium is removed?
abnormally increased cell proliferation
neural tube defects management approaches in utero
- prenatal surgery
- stem cell therapy
neural tube defects management approaches in infants
stem cell transplantation
neural tube defects management approaches in adults
surgery
etiology and pathogenesis of NTDs
- nutritional risk factors
- genetic risk factors
- environmental risk factors
this affects DNA methylation and histone modification
folic acid
mutation in this gene in animal models induces onset of NTDs
Pax
maternal exposure to teratogens
- arsenic
- pesticides
- drugs
teratogen that induces NTDs which is cytotoxic
arsenic
teratogen that induces NTDs which accumulates in the placenta
pesticides