Neural Crest Flashcards
BMP levels
regulate nervous system formation
- low level=nervous system
- high level=ectoderm
what surpressses BMP
near midline-noggin, chorddin, FGF
Neural crset fomration step
become distinct from adhjacent ectoderm and neural tissue
begin migration
localize and differentiate
Mapping neural crest fate
get quail cells, put in chick after remove that same part
let develop-see quail cells very different than chick
what does rostral mean
cranial
where does neural crest form
boundary where presumptive neural plat meets endoderm
- high levels of BMP on outside-epidermal
- the snail region have intermediate BMP
- neural plate-low bmp
snail tf
results in neural crest formation
- turns on genes that limit boundary between neural tube and boundary
- boarder specifer genes
boarer specifier gene functions
w/ bmps induce additional TF’s that speicify neural crest as well as genes for migration
-simulate c-kit and c ret-these genes have long migratory pathways
Iniitatin+ pathways of trunk neural crest migration
nueral crest much change epithelium to mesenchyme (EMT)
-lose 6b class of cadherins (mediate adhesion/in spot/belt desmosomes)-epi (tight pack) becomes mesenchyme (movable)
- Migrate into hyaluronic acid filed space
- GAGs in joints/embryos
steel factor+howw does neural crest move
produced in migratory pathways-c-kit receptor binds here
-hints at presence of ligand suggesting steel peptide is chemoattractant for receptor expressing cellls
-migratory pigment defects
ligand recepotr signalling system
hetero c-kit phenotype
migratory pigment defects+blood/germ cell defects
white spot on forehead/tummy
neural crest migration into gut
provides progenitors for enteric nervous system
Hirshbrungs disease-megacolon-deficeiny of enteric ganglia-cant excrete
How do NC cells migrate through gut?
ligand receptor system
recepotor=c-ret-on neural crest cells
ligand-GDNF-in gut
if can’t make it through, cret/GDNF mutants-NC cells need reach posterior gut
GDNF
chemoattractant of NC cells to colonize gut
GDNF production is activated sequentially in later time in more posterior gut
-gradient
hirshbrings disease
Hirshbrungs disease-megacolon-deficeiny of enteric ganglia-cant excrete
NC cells don’t make through colon to end
-cret/GDNF mutants
digeorge syndrome diagnosis, and etiology
cardiac/immune problems
low set, abnrmal ears
cleft pallete
defecits in several specific tissues
(pharyngeal and neurcal crest derivatives)
-represent failure of neural crest entering pharyngeal slits
-occur with large DNA deletion (same with mice/humans)
T box gene family
encode TFs
-such as brachyury-involved in mesoderm formation-posterior structures
tbx1 is maps onto DGS region
- expressed in pharynx and not NC cells=probably cause for lack of NC migration signals into pharynx
- knockout in mice had lowset ears
what regulates tbx1+ what does it regulate
SHH
targets peptides in FGF family
-loss of FGF family results in TGF like phenotype
crk1
anotehr contributor to DGS
-absence of crk1 via KO stops TGF/FGF signalling
also leads to NC migration problems
probably part of ligand that will look for a receptor in pharngeal slit cells
location of cork and tbx1
22q11-same spot!
fetal alcohol syndrome diagnosis and effects
mentally regarded
small openings between eyed
low nose bridge
smooth upper lip
congenital heart disease
causes pop of rostral parts of embryo
-espeically in NC cells-
what causes neural crest to deisperse/form
activation of sequenctial cascade of TFs started by specific BMP levels
What control NC migration
speicfic ligand receptor systems-secreted ligands are chemoattractants
alterations to nerual crest morphogenesis change
change in envrionemtn in which NC migrate (Tbx-1)
or efffect crest cell themselves (CrKL)
teratogen xposure and effect on neural precursors
affects neural precursors and neural crest survival-leads to dev deficiencies
LOOK AT HER SUMMARY-last slide
FOR ALL OF THE LECTURES
