Reiterated Wnt signaling during zebrafish neural crest development

While Wnt/beta-catenin signaling is known to be involved in the development of neural crest cells in zebrafish, it is unclear which Wnts are involved, and when they are required. To address these issues we employed a zebrafish line that was transgenic for an inducible inhibitor of Wnt/beta-catenin signaling, and inhibited endogenous Wnt/beta-catenin signaling at discrete times in development. Using this approach, we defined a critical period for Wnt signaling in the initial induction of neural crest, which is distinct from the later period of development when pigment cells are specified from neural crest. Blocking Wnt signaling during this early period interfered with neural crest formation without blocking development of dorsal spinal neurons. Transplantation experiments suggest that neural crest precursors must directly transduce a Wnt signal. With regard to identifying which endogenous Wnt is responsible for this initial critical period, we established that wnt8 is expressed in the appropriate time and place to participate in this process. Supporting a role for Wnt8, blocking its function with antisense morpholino oligonucleotides eliminates initial expression of neural crest markers. Taken together, these results demonstrate that Wnt signals are critical for the initial induction of zebrafish neural crest and suggest that this signaling pathway plays reiterated roles in its development.     

A gene regulatory network orchestrates neural crest formation

The neural crest is a multipotent, migratory cell population that is unique to vertebrate embryos and gives rise to many derivatives, ranging from the peripheral nervous system to the craniofacial skeleton and pigment cells. A multimodule gene regulatory network mediates the complex process of neural crest formation, which involves the early induction and maintenance of the precursor pool, emigration of the neural crest progenitors from the neural tube via an epithelial to mesenchymal transition, migration of progenitor cells along distinct pathways and overt differentiation into diverse cell types. Here, we review our current understanding of these processes and discuss the molecular players that are involved in the neural crest gene regulatory network.     

Spatio‐temporal control of neural epithelial cell migration and epithelium‐to‐mesenchyme transition during avian neural tube development

As opposed to the neural crest, the neural epithelium is generally viewed as a static and cohesive structure. Here, using an ex vivo system free of the environmental influences and physical constraints encountered in the embryo, we show that neural epithelial cells are on the contrary intrinsically motile, although they do not undergo spontaneous epithelium‐to‐mesenchyme transition and display molecular and cellular characteristics distinct from those of neural crest cells. However, they can be instructed to undergo epithelium‐to‐mesenchyme conversion independently of the acquisition of neural crest traits. Migration potentialities of neural epithelial cells are transient and are progressively restricted during neural tube development. Restriction of cell migration is irreversible and can be in part accounted for by increase in N‐cadherin in cellular junctions and in cell polarity. In conclusion, our study reveals that the neural epithelium is a highly flexible tissue in which cells are maintained cohesive under the control of a combination of extrinsic factors and physical constraints.