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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD039952-02
Application #
6592839
Study Section
Special Emphasis Panel (ZHD1)
Project Start
2002-05-01
Project End
2003-04-30
Budget Start
Budget End
Support Year
2
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Hung, Irene H; Schoenwolf, Gary C; Lewandoski, Mark et al. (2016) A combined series of Fgf9 and Fgf18 mutant alleles identifies unique and redundant roles in skeletal development. Dev Biol 411:72-84
Ellies, Debra L; Economou, Androulla; Viviano, Beth et al. (2014) Wise regulates bone deposition through genetic interactions with Lrp5. PLoS One 9:e96257
Lavine, Kory J; Ornitz, David M (2007) Rebuilding the coronary vasculature: hedgehog as a new candidate for pharmacologic revascularization. Trends Cardiovasc Med 17:77-83
Lin, Yongshun; Liu, Guoqin; Zhang, Yongyou et al. (2007) Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic morphogenesis and the acquisition of strict androgen dependency for adult tissue homeostasis. Development 134:723-34
Madsen, Erik; Gitlin, Jonathan D (2007) Copper and iron disorders of the brain. Annu Rev Neurosci 30:317-37
Vachharajani, Akshaya; Bethin, Kathleen; Mouillet, Jean-Francois et al. (2006) The rare occurrence of absent adrenals in a term infant: a case report and review of the literature. Am J Perinatol 23:111-4
Ellies, Debra L; Viviano, Beth; McCarthy, John et al. (2006) Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity. J Bone Miner Res 21:1738-49
Lavine, Kory J; White, Andrew C; Park, Changwon et al. (2006) Fibroblast growth factor signals regulate a wave of Hedgehog activation that is essential for coronary vascular development. Genes Dev 20:1651-66
Perlyn, Chad A; Morriss-Kay, Gillian; Darvann, Tron et al. (2006) A model for the pharmacological treatment of crouzon syndrome. Neurosurgery 59:210-5; discussion 210-5
Jacob, Anne L; Smith, Craig; Partanen, Juha et al. (2006) Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation. Dev Biol 296:315-28

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