Molecular Genetics Of Early Eye Development

National Eye Institute

Investigators

Linked publications, trials & patents

Abstract

The function of the homeobox gene Prox 1 was investigated in collaboration with several laboratories. Together with Dr. J. Wilting (Georg August University, Gottingen, Germany), we showed that Prox1 is a highly conserved transcription factor, expressed in hepatocytes from the earliest stages of development into adulthood and over-expressed in hepatoma cell lines. Its absence from bile duct epithelial cells suggested a function for the specification of hepatoblasts into hepatocytes. We demonstrated (in collaboration with Dr. E. Treuter, Karolinska Institute, Sweden) that Porx1 serves as a corepressor for Liver Receptor Homologue 1 (LRH1, NR5A2), a master regulator of cholesterol homeostasis in mammals. This study suggested that functional interactions between LRH1 and Prox1 may fulfill roles both during development of the enterohepatic system and in adult physiology. In collaboration with Dr. M. Duncan (University of Delaware), we demonstrated that basic leucine zipper transcription factors, Mafs, bind to the PL1 and PL2 elements, whereas Prox1 binds to the OL2 element in the chicken aB1-crystallin promoter. Furthermore, Mafs and Prox1 can stimulate chicken aB1-crystallin promoter activity. Pax6, a known negative regulator of aB1-crystallin gene expression, inhibits Prox1- and Maf-mediated transactivation by competitively binding all three elements. We proposed that Mafs, Prox1, and Pax6 collaborate to direct spatiotemporal expression of the chicken aB1-crystallin gene during lens development.