Developmental Neurobiology: Axon Guidance and Forebrain Patterning

As the brain develops, neurons extend axons over relatively vast distances to their targets. My laboratory uses zebrafish as a simple vertebrate system to study how axons navigate through the developing brain. Accessible and rapid early development, in combination with the ability to transplant cells between embryos, express genes both transiently and transgenically, and do genetic screens, makes zebrafish a powerful model system for the study of axon guidance.

We are characterizing several mutations that disrupt the ability of retinal axons to grow across the forebrain. Using a synteny cloning approach, we have identified the genes affected by the mutations you-too (yot) and detour (dtr). Both loci encode members of the gli family of transcription factors, proteins that are targets of early differentiation signals mediated by the secreted morphogen sonic hedgehog. These mutations disrupt cell differentiation in the ventral forebrain, including the pituitary. One focus of the lab is to understand the cellular cues disrupted in yot and dtr that normally guide axons across the forebrain, and to understand how midline signals direct the differentiation of these cells. A related goal is to determine the molecular and cellular mechanisms underlying axon defects in two other, more specific retinotectal mutations named belladonna and umleitung.

We ultimately hope to understand the cues that guide axons through their entire journey from eye to tectum. Toward this end, the lab will generate and characterize new mutants, taking advantage of the ability to visualize growing axons in live zebrafish embryos.

top