Growth control mechanisms that result in normal size and shape of body, organs and tissues requires complex integration of systemic, tissue and cellular mechanisms, and defects in these mechanisms can cause overgrowth and birth defects. Continuous growth of zebrafish and isometric growth of zebrafish fins with the body provide opportunities to better understand these growth control mechanisms. The unit of fin growth is the bony fin ray segment, which is added periodically to the distal end of the growing finds. Growth control mechanisms in dependently affect size of the new segment and rate of segment initiation, and mutations have been identified that alter segment size or bypass limits on segment initiation. Our goal is to understand how segments are initiate wild type fish and how limits on segment initiation are bypassed in mutant fish. Specifically, we will; (1) Use molecular markers for segment development to determine the relationship of segment initiation and (2) cell division, and whether segments are initiated synchronously in all fins (3) We will use cDNA microarrays to identify candidate genes expressed in intersegmentation phase, and use (4) these to determine whether overgrowth mutants rapunzel, long fin and primrose bypass intersegmentation (5) phase of fin growth. (3) We will identify the genes affected in the overgrowth mutants rapunzel and primrose, that bypass limits on segment initiation, and short fin, that results in shorter fin ray segments. In situ expression analysis of these gene wild type and mutant fish will provide insight which tissues or cells are involved regulating isometric growth in zebrafish fin. This work will have specific impact on understanding mechanisms of growth control in bone, and provide insight candidate genes and mechanisms involved in overgrowth syndromes in vertebrates and humans.
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