neural crest, ectoderm, epidermis

What acts as a morphogen to pattern the ectoderm

BMP

No BMP is due to what and forms what

Due to chordin and noggin and forms neural plate

High BMP is caused by what and forms what

Caused by no chordin/noggin and forms epidermis

Narrow region of ectoderm with intermediate BMP forms what

Neural crest

What happens when there is too much BMP

Neurulation and neural crest are distrupted

Noggin mutant

Lacks both neural plate and crest

Absence of BMP results in

Loss of both epidermis and neural crest

Where are ectodermal cells located

Junction of neural plate and epidermis

Fate mapping experiments

Fluorescently labeling NC cells prior to migration to track their movement

Neural crest cells undergo what and migrate where

Undergo EMT and migrate away to contribute to several tissues

PNS

Nerves and ganglia throughout the body

Neural crest development steps

1. Specification and differentiation

2. Further differentiation into destination fates

3. Migration to destination

Step one of neural crest development: specification and differentiation into neural crest

• occurs prior to migration

• Ectodermal cells are exposed to intermediate levels of BMP signaling which activates sox10

• Sox10 activates expression of further NC specific TFs (pax3/7)

• Expression of those TFs distinguishes NC from other ectodermal cells

Step 2 of neural crest development: further differentiation into destination fates

• occurs prior to migration

• Fates are linked to a-p axis position

• Sox10 works with hox genes to activate gene expression to specify unique fates in NC cells

• Unique gene expression in subpopulations of NC cells corresponds with eventual fate

Edn expression

Gene expressed in NC cells destined to become cranial melanocytes

C-ret expression

Migrates into gut to become PNS neurons

Results of cranial NC cells migrating into head and pharyngeal arches

Gives rise to melanocytes of head, facial bones, nerves of head/neck, glands in neck

Migration of cardiac NC cells

• forms melanocytes, nerves/ganglia of thorax, glands in neck

• Heart contributions: ventricular septum, outflow tract, septum

Migration of trunk NC cells

Migrate into and contribute to the PNS, adrenal medulla, melanocytes of trunk and limbs, trunk NC used to understand migration in general

Signals that initiate migration

• Rho: cytoskeleton changes for cell movement

• Snail: repression of cadherin expression

• NC cells express RhoB

What determines the path of migration

Local signals

What aids in migration

Tissues along the migration path express molecular “guideposts”

Signaling for melanoblast migration

• melanoblasts express receptors for attractive molecules called ephrins that are produced by the dermis

• Attractive interaction compels melanoblasts to migrate through dermis to epidermis

Signaling for adrenal medulla/gut PNS migration

Attractive signals from somites and dorsal aorta encourage cells to migrate ventrally

How do NC cells find their final destination

NC cells activate expression of different receptors to respond to their secreted attractive signals produced by destination tissues

Epidermis destination signal and receptor

NC cells destined to become melanocytes express the corresponding receptor (kit)

What does the epidermis secrete

CSF

Gut destination signal and receptor

• gut expresses GDNF

• NC cells destined to become enteric PNS express the corresponding receptor (Ret)

Disrupted development of neural crest

• defects called neurocristopathies

• Typically syndromes in which multiple disparate tissues are affected

Pigmentation neurocristopathies

• partial LOF mutations of heterozygosity in kit can disrupt melanoblasts causing pigmentation aberrations

MITF

NC cells fated to become melanoblasts express MITF prior to migration, MITF activates pigment production genes and promotes migration and prevents apoptosis

Treacher Collins syndrome

• genetic mutations that disrupt survival and proliferation of cranial NC

• Altered facial structure, hearing loss, etc

Hirschsprung’s disease

• mutations that disrupt GDNF-Ret signaling preventing NC cells from migrating into intestines to build gut PNS

• Patients lack innervations of portions of their colons and can cause “megacolon”

Neural crest/domestication hypothesis

• proposes that when breeders selected for reduced selection, they are selecting genetic variations that implant proliferation, survival, and differentiation of neural crest

• Explains why domestication that aims to “tame” animals is accompanies by unintended changed to face shape and pigmentation

• Defects in neural crest explain reduced aggression (decreased function of adrenal medulla which produces fight or flight hormones)