Neural crest cells are a migratory stem cell type
specified in the dorsal most region of the newly forming neural tube,
where they undergo an epithelial to mesenchymal transition
to delaminate out of this neural epithelium
and migrate away into the periphery
becoming any number of cell types from craniofacial elements
to enteric sensory neurons.
This figure captures the process of neural crest delamination
at the time when the neural and surface ectoderms have separated
and are in the process of fusing at the midline
into the neural tube and epidermis, respectively.
A dorsal to ventral gradient of BMP and Wnt signals
specify the three major regions of the neuroepithelium,
leading to their expression of unique adhesion proteins.
Specifically, the surface ectoderm will express E-cadherin
while the neural tube is marked by N-cadherin expression,
and the premigratory neural crest express cadherin-6B.
The premigratory neural crest domain
experiences some of the highest levels of BMP expression
paired with more intermediate amounts of Wnt signals,
this combined morphogen exposure
supports the differential expression of Snail-2
and in particular its upregulation in these neural crest cells.
This is a pattern of Snail-2 expression reinforced
by the inhibitory actions of Sox2 in the neural tube.
Snail-2 protein functions to repress cadherin expression,
which results in the weakening cell-cell adhesions
as well as restricting the localization of Cadherin-6B
only to the apical half of premigratory neural crest cells.
This asymmetric expression of Cadherin-6B
in turn functions to polarize the activation of RhoA
and actomyosin contractile fibers needed for apical constriction
and the initiation of delamination.
As neural crest cells delaminate from the neuroepithelium
they will contact one another,
which is an event that will trigger a behavior of contact inhibition.
Contact inhibition will cause the two cells to stop, turn,
and then migrate away in the opposite direction.
It is known that non-canonical Wnt signaling reinforces
the polar activity of RhoA and Rac1
along the pathway of migrating neural crest cells.
Taken together the morphogen metered expression of adhesion proteins
creates the spatially targeted development of neural crest cell specification,
which leads to the polarized streams of bilaterally migrating neural crest cells.