Development of Neural Crest Flashcards Preview

BMS 2 Week 3 > Development of Neural Crest > Flashcards

Flashcards in Development of Neural Crest Deck (14):
1

Levels of BMP regulate nervous system formation from ectoderm 

  1. Low levels of BMP at midline allow nervous system to form
    1. BMP levels are kept low by upregulation of FGF, Noggin, and Chordin
  2. Intermediate levels of BMP are associated with neural crest cells which help differnetiate between nervous system and epidermis
  3. High levels of BMP associated with continued maintenence of ectoderm which will turn into epidermis 

2

Cranial or Rostral derivatives of neural crest cells 

  1. Neurons and Glia 
  2. Cartilage and Bone
  3. Connective tissue
  4. Most of cranial face 

3

Caudal or trunk neural crest cells give rise to 

  1. Pigment cells
  2. Sensory neuron cells in glia
  3. Sympathetic cells 
  4. Enteric nervous system 

4

Process of Neural Crest Formation 

  1. Intermediate levels of BMP and Snail transcription factor activated
  2. Snail activates multiple border specific transcription factors activated
  3. These then activate Neural crest specifier transcription factors such as Sox10
  4. Sox10 then stimulates production of specific receptors important in migratory pathway
    1. NC expressing C-kit receptor destined for germ cells, pigment cells, and hematopoetic cells 
    2. NC expressing C-ret receptor destined for eneteric nervous system 

5

Initiation and pathway of trunk neural crest migration 

  1. NC transition from epithelia to mesenchyme through loss of 6B class of cadherins
  2. NC migrate into hyaluronic acid filled space 

6

C-Kit receptor on NC and Steel Factor Ligand in environment 

Receptor-ligand used for:

  1. germ cells
  2. hemopoetic cells
  3. NC-derived pigment cells

Receptor-ligand interaction

  1. NC produce C-kit receptor
  2. Steel factor ligand produced in migratory pathway 
    1. Steel peptidue functions as a chemoattractant for C-kit receptor expressing cells. 

    *Humans heterozygous for C-kit mutation have migratory deficities in pigment (white spots), hemopoetic, and germ cell migration. 

7

C-ret receptor and GDNF 

Receptor-ligand used for:

  1. Development of enteric nervous system of the gut 

Receptor-ligand interaction

  1. NC produce C-ret receptor
  2. GDNF produced in sequentally activated in migratory pathway first more rostrally and then more caudally and acts as a chemoattractant for NCs expressing C-Ret
    1. Once cells get to a certain point in the gut, there is a second source 

Hirschprung's disease

-Migration of neural crest cells into gut provides progenitors for the enteric nervous system 

-In HD, C-ret or GDNF mutations prevent NC cells from migrating appropriately to give rise to the enteric ganglia resulting in inhibition of peristalsis. 

-By neonatal stage, there is instance of megacolon 

      *side effect of deficiency in enteric ganglia that prevent gut from emptying 

 

8

DiGeorge Syndrome (DGS)

  1. Cardiac outflow tract & septal defects--severe
  2. Thymus and parathryoid hypoplasia--immune def.
  3. Laryngeo-trachial anomalies
  4. Craniofacial anomalies/facial dysmorphogenesis
  5. Cleft palate
  6. Micrognathia (small jaws)
  7. Low-set, abnormal ears

9

Migration of NCs into Pharyngeal System 

  1. NCs come in from top of neural tube to enter region of pharynx
  2. NC will enter pharyngeal arches and give rise to several structures such as thymus, parathyroid, and cardiac outflow tract 

*Since DiGeorge syndrome 

-Have problems in Neural crest derivatives such as thymus, parathyroid, cardiac outflow tract

-Have problems in Pharyngeal arch and pouch derivatives such as larynx and pharynx 

-Hypothesis is that both NC and Phaynx mutations could be involved. 

-Experiment revealed that Tbx1 gene mutation in Pharynx cells prevented proper migration of NCs and resulted in DiGeorge Syndrome. 

10

Chromosomes containing mutated genes in DiGeorge Syndrome in Human and Mouse 

DGS region is 22q11 in human

DGS region in ch16 in mouse 

11

Tbx1  and DiGeorge Syndrome 

  1. Shh activates a cascade that causes activation of transcription of Tbx-1 gene to form Tbx-1 transcription factor in pharynx cells 
  2. Tbx-1 transcription factor bind to 5'regulatory domain of FGF family genes and activate them. 
  3. FGF signaling allows proliferation of pharyngeal tissue 
  4. Allows NCs to migrate there, survive, and be maintained properly. 

*Mutations in Tbx-1 causes DiGeorge Syndrome 

12

Crkl and Di George Syndrome 

  1. Crkl gene encodes an adaptor protein on NCs. 
  2. When FGF signal is sent out by Pharynx cells, Crkl adaptor protein on NC binds to FGF and TGF-B and migrates. 

DiGeorge Syndrome 

Mutations in Crkl gene cause mutations in adaptor protein which prevent binding to FGF or TGF-B. 

Results in severe defects in cardiovascular patterning. 

13

Fetal Alcohol Syndrome 

  1. Scientists have done this where in the mouse during embryonic week 7, they have added alcohol

  2. Few hours after alcohol was added, you will start seeing effects on the face. There is absence of midline structures, smaller nose that are characteristic of FAS

14

Effects on Neural Crest Cells when exposed to alcohol 

Expose mouse to alcohol at stage when neural folds are forming and neural crest cells start to migrate

-NC migration deficient

-Much apoptosis in NC cells

-Reduced contribution to nasal and maxillary processes and you induce facial malformations