Neural Crest Flashcards
Neurulation occurs when ____ at the midline dives down to form ____ ____. _____ activity is suppressed at the midline by noggin and chordin.
- Epidermis, which is lateral to the ___ ___ has high [___]
- The neural crest in the midline has intermediate [__]
Neurulation occurs when ECTODERM at the midline dives down to form NEURAL TUBE. BMP activity is suppressed at the midline by noggin and chordin.
- Epidermis, which is lateral to the NEURAL TUBE has high [BMP]
- The neural crest in the midline has intermediate [BMP]
Cranial and trunk derivatives of neural crest
Neurons and glia of cranial ganglia Cranial cartilage and bone Cranial connective tissue Enteric nervous system Sympatho-adrenal cells Sensory neurons and glia Pigment cells
Neural crest forms at boundary where ____ ___ meets ectoderm.
Intermediate levels of ____ in conjunction with ____ and other molecules induce ____ and then ____-specifier TF genes (___ for pigment cells, ____ for enteric neural precursors) just at this boundary. ___ is induced by intermediate levels of ____.
These genes, in conjunction with ___ and ___, then induce additional downstream ___ ___ that specify the neural crest as well as genes used in ___.
___ is the TF that stimulates previously mentioned TFs.
Neural crest forms at boundary where NEURAL PLATE meets ectoderm.
Intermediate levels of BMP in conjunction with FGF and other molecules induce SNAIL and then BORDER-specifier TF genes (C-KIT for pigment cells, C-RET for enteric neural precursors) just at this boundary. SNAIL is induced by intermediate levels of BMP.
These genes, in conjunction with BMP and WNT, then induce additional downstream TRANSCRIPTION FACTORS that specify the neural crest as well as genes used in MIGRATION.
SOX10 is the TF that stimulates previously mentioned TFs.
Initiation and pathways of trunk neural crest migration:
- NC must undergo ____—->____ transition by losing _______.
- Need migratory space, so cells secrete ______
- Two major migratory pathways
A. Through ___ under most superficial layer which gives rise to ____
B. Go between ___ ___ and _____.
Initiation and pathways of trunk neural crest migration:
- NC must undergo EPIDERMAL—->MESENCHYMAL transition by losing 6B CADHERINS.
- Need migratory space, so cells secrete HYALURONIC ACID.
- Two major migratory pathways
A. Through ECTODERM under most superficial layer which gives rise to MELANOCYTES
B. Go between NEURAL TUBE and SOMITES.
______ receptor (a ____ receptor) is expressed on _____ cells, along with ___ _cells, ____ cells, and _____ cells.
The receptor binds _____ ____ ligand, which is produced in migratory pathways of these cells. It functions as _____ for ____-expressing cells. If ____ is not present, migration is defective.
C-KIT receptor (a TYROSINE-KINASE receptor) is expressed on MIGRATORY cells, along with GERM cells, HEMATOPOIETIC cells, and NC-DERIVED PIGMENT cells.
The receptor binds STEEL FACTOR ligand, which is produced in migratory pathways of these cells. It functions as CHEMOATTRACTANT for RECEPTOR-expressing cells. If STEEL FACTOR is not present, migration is defective.
Neural crest migration into gut:
- Migration of neural crest into gut provides progenitors for ____ ____
- In humans ______ disease is the major congenital abnormality of the gut and is characterized by ____ ____., causing deficiency of ____ ____, which causes constipation.
Neural crest migration into gut:
- Migration of neural crest into gut provides progenitors for ENTERIC NERVOUS SYSTEM
- In humans HIRSCHPRUNGS disease is the major congenital abnormality of the gut and is characterized by MEGACOLON., causing deficiency of ENTERIC GANGLIA, which causes constipation.
Ligand-receptor system that contributes to migration of NC cells through the gut
____ (receptor) is expressed in neural crest cells while ____ (ligand) is expressed in gut. The ligand serves as _____ for NC cells. The stomach makes it, it trickles down the GI system, but then subsequent _____ occurs at ____ ____, causing a gradient.
In double-gene mutants, NC migration never ____ ___ ___.
_____ mutations are also associated with _____ disease, where ___ enteric ganglia do not form.
Ligand-receptor system that contributes to migration of NC cells through the gut
C-RET (receptor) is expressed in neural crest cells while GDNF (ligand) is expressed in gut. The ligand serves as CHEMOATTRACTANT for NC cells. The stomach makes it, it trickles down the GI system, but then subsequent EXPRESSION occurs at SECONDARY SOURCE, causing a gradient.
In double-gene mutants, NC migration never REACHES POSTERIOR GUT.
C-RET mutations are also associated with HIRSCHPRUNGS disease, where DISTAL enteric ganglia do not form.
DiGeorge Syndrome Symptoms
- cardiac outflow tract and septal defects
- thymus and parathyroid hypoplasia (immune deficiency)
- laryngeo-trachial anomalies
- craniofacial anomalies
- cleft palate
- micrognathia
- low set ears
Etiology of DiGeorge Syndrome
- multiple lineages affected
- deficits seen in ____ ___ and ____ ____ derivatives
- also deficits in ____ ___ derivatives (____, ____, ____ tract cells in ___)
-____ is expressed in all cell types of ___, but NOT in ____ ___ ____ cells.
Etiology of DiGeorge Syndrome
- multiple lineages affected
- deficits seen in PHARYNGEAL ARCH and PHARYNGEAL POUCH derivatives
- also deficits in NEURAL CREST derivatives (THYMUS, PARATHYROID, OUTFLOW tract cells in HEART)
-TBX1 is expressed in all cell types of PHARYNX, but NOT in MIGRATING NEURAL CREST cells.
What regulates Tbx-1?
- Upstream: ____
- Tbx-1 targets include _____ family genes. Tbx-1 binds ___ ____ regions in these genes.
- If ____ is diminished in ____ expression domain, phenotype is similar to Tbx1 mutant
Tbx-1 induces ____, which help migrating NC cells when they reach the ____ region to survive and give rise of patterning in that region.
What regulates Tbx-1?
- Upstream: Shh
- Tbx-1 targets include FGF family genes. Tbx-1 binds 5’ REGULATORY regions in these genes.
- If FGF is diminished in TBX1 expression domain, phenotype is similar to Tbx1 mutant
Tbx-1 induces FGF, which help migrating NC cells when they reach the PHARYNGEAL region to survive and give rise of patterning in that region.
Alternative causative gene in Digeorge’s Syndrome:
____, which is also near the ______ region is an adaptor protein implicated in ____ and ____ signaling
-____ is expressed in neural crest cells, in contrast to ____, which is not.
-____ is sometimes deleted in DiGeorge’s
-absence of ____ impairs ____/___ Signaling which leads to severe defects in ______ patterning, which is NEURAL CREST SPECIFIC, while the _____ derivatives are normal
Alternative causative gene in Digeorge’s Syndrome:
CRKL, which is also near the 22Q11 region is an adaptor protein implicated in FGF and TGF-B signaling
-CRKL is expressed in neural crest cells, in contrast to TBX1, which is not.
-CRKL is sometimes deleted in DiGeorge’s
-absence of CRKL impairs FGF/TGF-B Signaling which leads to severe defects in CARDIAC patterning, which is NEURAL CREST SPECIFIC, while the PHARYNGEAL derivatives are normal
Fetal Alcohol Syndrome Symptoms
Alcohol causes _____ in NC cells
- short palpebral fissues
- low nose bridge
- maxillary hypoplasia
- smooth philtrum
- congenital heart disease
Alcohol causes APOPTOSIS in NC cells
