Specification of the Zebrafish Ventral Neural Tube

Carnegie Institution Of Washington, Washington DC

Investigators

Abstract

0080087 Halpern Analyses of mutations that affect early development of the zebrafish embryo indicate that specialized cells that lie at the ventral midline of the neural tube, comprising the floor plate, are specified earlier than previously thought. Moreover, recent work has implicated the TGF-b-related signal nodal encoded by the zebrafish cyclops gene in floor plate induction. Dr. Halpern's previous work demonstrated that Cyclops signaling in the early organizer region of the gastrula is critical for restoration of the floor plate and ventral brain in the cyclops mutant central nervous system (CNS), which normally lacks these cells. The goal of this project is to study how nodal signaling effects changes in cell behavior and cell fate that lead to floor plate differentiation. One approach is to define in greater detail the spatial and temporal requirements for ventral neural tube rescue in cyclops mutant embryos. A simple paradigm has also been devised to study the response to signaling at the single cell level, taking advantage of the finding that the One-eyed pinhead protein is a critical cofactor for responsiveness of cells to nodal signals. Using this assay, she will assess directly whether Nodal-related factors are floor plate inducing signals by monitoring the properties of inducing and responding cells. A related goal is to explore further the role of hedgehog genes in specification of the ventral neural tube. Although Sonic hedgehog is thought to be the floor plate inducing signal in vertebrate embryos, mutations of the zebrafish orthologue do not affect development of the CNS ventral midline. Through the generation of mutations, we aim to determine whether the hedgehog-related protein Tiggy-winkle, either alone or in combination with Sonic hedgehog, functions in determination of floor plate in the zebrafish. Through these studies she will gain a greater understanding of the early-acting mechanisms that pattern the developing nervous system.