Building and shaping the central nervous system in higher vertebrates: an integrative approach. (360G-Wellcome-088380_Z_09_Z)

In spite of its fundamental and medical significance, the morphogenesis of the early central nervous system of the amniote embryo remains poorly understood. I propose an integrated study of amniote neurulation as a dynamic process, which is now possible in the chick embryo. Using multi-photon, high-resolution imaging in intact embryos (Nature 449: 1049) and precisely controlled gene targeting methods (Nat Protoc 3: 410) I have recently developed, we will first analyse the global flow of ce ll movements and characterise individual cell behaviours underlying morphogenesis of the early neural tissue. This will allow formulating precise hypotheses on the determinants in this process (cell movements and cell growth), which will be tested functionally. The data from these reductionist approaches will be incorporated into a computer model of the early neurula to understand the shaping of the whole tissue and embryo. In parallel, we will study the naturally occurring stem cells that b uild the main embryonic axis, including the posterior neural plate and axial structures. High-resolution imaging and other direct methods will be used to determine their mode of renewal and the lineage relationships, and we will undertake the molecular characterisation of these cells to study their establishment and differentiation.