The formation of the vertebrate nervous system begins in early embryonic development when one portion of the embryo, the ectoderm, is divided into neural and epidermal tissue. The division of ectoderm into these two developmental fates is dependent on cell-cell interactions that control both the morphology and differentiation of ectodermal cells. These interactions cause a boundary to form between neural and non neural ectoderm, and allow ectoderm to form neuroepithelial cells which give rise to neural cell types. These are the events that underlie the formation of the neural tube, a process in which defects readily occur in human development. These abnormalities lead to syndromes know as neural tube defects, of which spina bifida is a well known example. To study these events, several approaches have been taken to identify cell surface molecules that underlie the cell-cell interactions necessary for early neural development in Xenopus embryos. One approach has been to identify molecules that mediate adhesion between embryonic cells by a calcium-dependent, homotypic binding mechanism. This approach has identified a class of cell adhesion molecules, called the cadherins, that are expressed in ectoderm when it separates into epidermal (E-cadherin) and neural tissue (N-cadherin). The present proposal is to analyze the developmental role of the cadherins in the formation of epidermal and neural tissue using various techniques to perturb the expression of these molecules in early Xenopus embryos. A second approach has been to identify Xenopus homologs for genes that have been identified through genetic studies of neurogenesis in Drosophila. embryos. This approach has identified a Xenopus homolog to the Drosophila Notch gene. Notch is a large cell surface glycoprotein which mediates cell-cell interaction that are necessary for the generation of neural tissue from the embryonic epithelium in Drosophila embryos. The Xenopus homolog of Notch is being studied to determine if it has a similar role in the formation of neural tissue in Xenopus embryos.
| Mah, S P; Saueressig, H; Goulding, M et al. (2000) Kidney development in cadherin-6 mutants: delayed mesenchyme-to-epithelial conversion and loss of nephrons. Dev Biol 223:38-53 |
