Neural crest Cells
NCC are pluripotent cells
These leave the neuroectoderm and may undergo
Epithelial-mesenchymal transition
Migration of pigment cells from
neural crest in dt-Wagethe rat
embryo after 18 days
(adapted from Wenner 1961)
• Pigment cells,
Domains • sensory ganglia
Forebrain & Midbrain frontonasal process,
palate, incus, malleus, jawbones
• parasympathetic ganglia
• hormone-producing cells •Bones & CT of the head
• glia cells •Certain structures within the eyes,
ears and teeth
Cardiac NC Melanocytes, neurons, cartilages, CTs
•Melanocytes
--------------- > Schwann cells, adrenal medulla
•Dorsal root ganglia
•Sympathetic ganglia
•Parasympathetic ganglia
Cranial NCC branchial arches, face
& neck
Vagal NCC ( S 1-7)
Sacral NCC ( posterior to S28)
parasympathetic nerves of gut
Cardiac NCC (S 1-3) septum between
PA & Aorta
Trunk NCC (6 to tail) sympathetic neurons
(S18-24) adrenal medulla
Migratory paths of NCC in the head region
NCC leave the crests area of the neural folds prior to neural tube closure
and migrate to form structures in the neck and face, pharangeal arches (1-6)
Epibranchial placodes (V,VII, IX and X)
Cranial NCC from rhombomere regions
• R 1&2 migrate to the 1st pharyngeal arch
jawbones, ear bones, frontonasal process
• R4 migrate to the 2nd pharyngeal arch
hyoid cartilage
• R6 migrate to the 3rd & 4th pharyngeal arch and pouches
thymus, parathyroid, thyroid
R 3 & 5 do not migrate thru the surrounding mesoderm but on
either side of the rhombomere mesoderm
Concentration of BMPs
(junctional border of surface ectoderm neural plate)
High level induces epidermis formation
Intermediate level induces neural crest cells formation
Low level induces neural ectoderm formation
Regulation of NCC Induction
Intermediate concentration of BMPs
(together with FGF and WNT proteins)
induce
PAX3 & other transcription factors
that specify the neural plate border
induce
2nd wave of transcription factors:
SNAIL and FOXD3 which specify cells as neural crest
SLUG which promotes NCC migration from neuroectoderm
How is migration initiated?
• BMP 4 & 7 induce RhoB & Slug genes
( protein products)
Establish cytoskeletal Activate factors that
conditions that promote dissociate the tight junction
migration in between the cells
• Loss of N-cadherin that links neural crest cells
How do migratory agents know the route on which
to travel?
1) Path of NCC is controlled by Extracellular matrix
ECM proteins
Promote migrations Restrict migrations
Exs: Ex:
Fibronectin Ephrin proteins
laminin (expressed in the posterior
Tenascin, portion of sclerotome)
collagen molecules
proteoglycans
2) Chemotactic and maintenance factors
- soluble factors secreted by potential destinations
Ex: stem cell factors
(allow continuous proliferation of NCC )
Final differentiation of Trunk NCC
• Determined by the environment into which they migrate
and settle
cell signaling factors:
TGF-β superfamily
Growth factors
Exs: 1) BMP2 (secreted by the lungs, heart, dorsal aorta):
NCC cholinergic neurons sympathetic ganglia
2) Endothelin-3
NCC melanocytes
NCC adrenergic neurons in the gut
3) Glucocorticoids : NCC adrenomedullary cells
4) FGF : NCC sympathetic neurons
What specify the fates of NCC?
• Combination of Hox genes
(the genes that specify A-P axis )
Hox genes appeared with the task of organising the body plan of an animal
Hox genes are a particular subfamily of homeobox containing genes that evolved
together with a complex multicellular body plan.
They have been utilised to convey positional information and organise the body
plan
3 Features of Hox genes.
1. They contain a sub-class of highly conserved homeobox sequences, so
they
encode transcription factors.
2. They are involved in organising the body plan of an animal.
3. They exist in clusters of similar genes in the genome.
Hox genes have the task of organizing the body plan of an animal
Hox genes are a particular subfamily of homeobox containing
genes that evolved together with a complex multicellular body
plan.
They are utilized to convey positional information and
organize the body plan
3 Features of Hox genes.
1. They contain a sub-class of highly conserved homeobox
sequences, so they encode transcription factors.
2. They are involved in organizing the body plan of an animal.
3. They exist in clusters of similar genes in the genome.
