The development of complex organs from pre-structural tissues is a mysterious process. Transdifferentiation and organ specialization depend on an interaction of biologic events which move rapidly in the assembly of structure-function relationships in the growing embryo. Cell differentiation is an active process and this suggests an on-line role for gene modulation. We believe that organ development depends on the participation and continuity of sequential sets of transcriptional proteins responding to morphogenic cues. Such developmental programs are restrictive, decisional, and usually tissue-specific. Very few pieces of this regulatory puzzle are known, and we believe a program project such as ours will cultivate new interdisciplinary research in this area. The projects in our program portfolio collectively bridge the disciplines of genetics and biochemistry with basic pathophysiology in support of six established research laboratories with common interest in the developmental biology of amniotes. Each of the project leaders come from diverse career pathways and bring special interactive strengths to the larger group. All of our projects are initially focused on rodents. Project 1 will identify new Kruppel-type zinc fingers expressed in the early stages of kidney development; Project 2 will focus on the comparison of genetic programs regulating hepatic development and regulation; Project 3 will investigate the effects of perturbations of Connexin 43 (Cx43) on the expression of gap junction proteins during the differentiation of nephrons; Project 4 will evaluate the role of forkhead domains in transcription factors that are active in early nephrogenesis; Project 5 will identify the genes important in the differentiation of adipose tissue using retinoic acid as a morphogen to probe the conversion of preadipocytes; and Project 6 will examine the molecular actions of caudal- related homeodomain proteins in the endoderm of developing intestine. Core units for project administration, molecular biology, and embryologic histochemistry will provide necessary and appropriate infrastructure. It is our hope and expectation that our work will successfully identify the positional coordinates for some important regulatory events by beginning an intensive study of significant genes in early organ development.
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