BMP SIGNALING IN THE SPECIFICATION OF NEURAL CELL TYPES.

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

DESCRIPTION (provided by applicant): The objective of this proposal is to understand how, when, and where BMP signaling specifies dorsal cells of the zebrafish neural tube. In zebrafish BMP mutants, neural crest, dorsal sensory neurons, and interneurons display aberrant phenotypes ranging from complete loss to dramatic expansion. We hypothesize that dorsal cells are specified within different ranges of BMP activity during early gastrulation. To determine whether dorsal neural cells are specified within a range of BMP activity, BMP signaling activity will be modified in wild type and BMP mutant embryos by injecting mRNAs encoding BMP agonists or antagonists. If cells are specified within a range of BMP activity, neural crest, dorsal sensory neurons, and interneurons may be expanded when BMP activity levels are reduced within their threshold, and may be lost when BMP activity is reduced below the threshold required for specification. Transgenic fish carrying a heat-inducible BMP agonist or antagonist constructs will be utilized to address when in development BMP activity is required for the specification of dorsal cells. Heat-shock activation at different developmental time points will determine if BMP signaling is required during and/or after gastrulation stages. Heterochronic cell transplantation studies will also be used as an alternative method to dissect when signals are required, and will provide additional information about where signals are required. Finally, an in situ mutagenesis screen will be performed to identify embryos defective in the specification of dorsal sensory neurons and/or interneurons. Such a screen may reveal novel molecules essential for specification of these cell types.