Dermal Bone Growth in the Zebrafish

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DESCRIPTION (provided by applicant): The long-term goals of this proposal are to elucidate the mechanisms of dermal bone growth and development. Studying the role of dermal bone growth genes in mammals is difficult due to the complex morphology of the craniofacial and cranial vault bones. Therefore, this proposal will utilize the properties of the zebrafish fin skeleton to examine the growth and development of dermal bone. Growth of the bony parts of the zebrafish fins (fin rays) is achieved by the distal addition of bony fin ray segments. The short fin (sof) mutation produces fin ray segments that are approximately half the length of wild-type segments. Therefore, the first aim of this proposal is to reveal the molecular basis of segment growth by cloning the sof mutation and characterizing its function. The second aim is to develop a spatial-temporal model for segment assembly (growth) by comparing the expression patterns of the signaling molecules shh, ptc1, and bmp2 with one proven growth marker (as a spatial reference) and with a presumptive joint marker (as a temporal reference). Once this is established, other fin growth markers may be added to this model. These growth markers will be identified by microarray analysis in the third aim, characterized as reliable markers, and then added to the model for segment growth. Since the genes identified by the microarray represent genes expressed during segment growth, their expression will also be analyzed in five different segment length mutants (including sof). Finally, to enhance the morphological analyses, a larger collection of new mutations causing short fins will be generated by a sof enhancer screen in the fourth specific aim. By completing these aims, this proposal will provide new insights of direct relevance for understanding the biology of human malformations.