COREGULATION OF ALK8 AND BMP4 IN ZEBRAFISH TOOTH FORMATI

Forsyth Institute, Cambridge MA

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Abstract

Although the stages of zebrafish development have been well documented, the molecular mechanisms underlying the cellular movements, proliferation and differentiation are not well defined. The zALK-8 (zebrafish Activin Receptor-Like Kinase) gene predicts a protein with a serine/threonine kinase domain similar to other TGF-beta superfamily receptors. Initial characterization of partial genomic clones revealed a conserved intronic sequence between zALK-8 and the zebrafish BMP-4 (Bone Morphogenic Protein) gene. Preliminary immunohistochemical analysis indicates that zALK-8 is developmentally regulated and is coordinately expressed with zBMP-4 during tooth development, positioning it well to play a role in tooth development. We hypothesize that the coordinate expression of zALK-8 and zBMP-4 is essential for normal tooth development. We propose the following specific aims to test this hypothesis. First, we will fully characterize the promoter and intronic sequences of zALK-8 gene to facilitate identification of regulatory domains. Promoter sequences and other conserved domains will then be examined in reporter constructs to identify potential enhancer regions and binding domains for cis-acting elements. The coordinate expression and regulation of the zALk-8 and zBMP-4 genes in tooth development will be examined using reporter constructs of GFP for zALk-8 and YFP for zBMP-4 allowing easy visualization of overlapping and distinct domains of expression.