premigratory neural crest cells
cells at the regional interface are the neural plate border and have different specification
- as neural folds comes together, pre-migratory neural crest cells undergo EMT while neural tube and epidermal epithelia unite
- post EMT, migratory neural crest cells move throughout the developing embryo
the Wnt/BMP code sets up expression of EMT regulatory factors that drive delamination of neural crest
-premigratory neural crest cells differentially express Cadherin-6B
-Wnt/BMP signaling promotes delamination (material fractures into layers) by upregulating EMT factors like Snail-2
- Snail 2 transcription factor downregulates Cadherin-6B and tight junction proteins, promoting de adhesion
-delaminating neural crest cells exhibit contact inhibition (change their direction of migration upon contact with another cell) of migration, helping cells to spread out during EMT
How are neural crest cells specified?
- neural crest cells are specified at the neural plate boundary, suggesting that intermediate BMP signals may be important in this specification
-intermediate levels of BMP signaling in the context of continuous Wnt signaling produces neural crest
-this combinatorial signaling activates transcription factors that first specify the neural plate border, which in turn activate neural crest specifiers
neural crest cells are multipotent progenitors
neural crest cells migrate throughout the embryo and develop into a variety of cell types and structures
-however, neural crest cells have different properties/potentials that depend upon their origin
four major subdivisions of neural crest
(1) cranial
(2) cardiac
(3) trunk
(4) vagal and sacral
neural crest is derived all along the A/P axis
the differential potentials of different types of neural crest seem to be due to differential Hox gene expression along the A/P axis
cranial neural crest
these cells can become the same types of cells as trunk neural crest, but cranial can also form bone, cartilage, and connective tissue (mesoderm like)
-vertebrate head is largely comprised of neural crest derivatives
- midbrain, rhombomeres, jaw, middle ear bones, neurons of the teeth and eye, neck cartilage, facial nerves, etc
cardiac neural crest
forms part of the heart and arteries
-contribute to arteries of the aortic arch and the septum between the aorta and pulmonary artery
- cardiac cells also contribute to the thyroid, thymus, and parathyroid glands
trunk neural crest
migrate through either a dorsal or ventral pathway
dorsal; form pigment cells (melanocytes) and migrate between the dermis and epidermis, enter the ectoderm, and colonize the skin and hair follicles
ventral: becomes sensory and other neurons of the peripheral nervous system and glia; the cells move ventrally through the anterior sclerotome (somite mesoderm that forms spine cartilage)
neural crest migration routes are directed by extracellular cues
- early migrating trunk neural crest is forced ventrally by several cues, such as Ephrins, becoming neurons
- ventral neural crest initially move between somites, but this is then blocked by Semaphorin-3F
- this forces neural crest to migrate through somites
- this migration is restricted to the anterior of the somite by anterior permissive signals;(fibronectin and laminin) and posterior blocking signals (Ephrins, Semaphorin 3F)
- later migrating cells switch to traveling dorsally and become pigment cells
- the switch is due to down regulation of transcription factor Foxd3, which allows expression of MITF, a transcription factor that specifies melanoblasts
- melanoblasts up regulate Ephrin receptor EphB2, which allows for migration along Ephrins
