Patterning the zebrafish central nervous system.

We have described the formation of the zebrafish central nervous system. The spinal cord has the simplest organization and was considered first, followed by the forebrain, midbrain and hindbrain. We have discussed many studies that have revealed the molecular mechanisms, including extrinsic signals and intrinsic responses to them, underlying the establishment of nervous system regions and the wide diversity of neuronal cell types of which they are comprised. Wherever possible, we have tried to compare what has been learned from zebrafish with what is known in other vertebrate species. The simplicity of the developing nervous system makes zebrafish embryos particularly amenable to studies of nervous system development. Thus, many aspects of nervous system patterning that were unknown from other vertebrates have been revealed by studies in zebrafish. However, the relationship between embryonic and adult nervous system morphology is still not entirely clear and remains an important avenue for further studies.

parachute/n-cadherin is required for morphogenesis and maintained integrity of the zebrafish neural tube.

N-cadherin (Ncad) is a classical cadherin that is implicated in several aspects of vertebrate embryonic development, including somitogenesis, heart morphogenesis, neural tube formation and establishment of left-right asymmetry. However, genetic in vivo analyses of its role during neural development have been rather limited. We report the isolation and characterization of the zebrafish parachute (pac) mutations. By mapping and candidate gene analysis, we demonstrate that pac corresponds to a zebrafish n-cadherin (ncad) homolog. Three mutant alleles were sequenced and each is likely to encode a non-functional Ncad protein. All result in a similar neural tube phenotype that is most prominent in the midbrain, hindbrain and the posterior spinal cord. Neuroectodermal cell adhesion is altered, and convergent cell movements during neurulation are severely compromised. In addition, many neurons become progressively displaced along the dorsoventral and the anteroposterior axes. At the cellular level, loss of Ncad affects beta-catenin stabilization/localization and causes mispositioned and increased mitoses in the dorsal midbrain and hindbrain, a phenotype later correlated with enhanced apoptosis and the appearance of ectopic neurons in these areas. Our results thus highlight novel and crucial in vivo roles for Ncad in the control of cell convergence, maintenance of neuronal positioning and dorsal cell proliferation during vertebrate neural tube development.