How do multiple cell types coordinate their development to build an organ? This question can be addressed by studying development of the C. elegans gonad, a relatively simple organ comprised of an epithelial tube (gonad arm) with discrete specialized compartments (i.e. uterus and spermathecae in hermaphrodites). Preliminary evidence shows that pha-4, the only C. elegans homolog of the foxA vertebrate transcription factor family, plays an important role in gonad development. pha-4 has previously been shown to be critical for development of all cell types in the pharynx. How does one transcription factor regulate distinct gene expression in different cell types and organs? One hypothesis is that different co-factors regulate pha-4 function at distinct times and locations during development. In support of this hypothesis, CHW-1 has been identified as a putative PHA-4 binding factor, and preliminary evidence shows that pha-4 and chw-1 genetically interact during gonad development. In this proposal the following experiments are described with the goal of understanding the roles of pha-4 and chw-1 in gonadogenesis: to identify when and in which gonad cell types the two genes function, to determine if CHW-l binds PHA-4 in vitro, to characterize genetic interactions, and to define how chw-1 modifies pha-4 activity. These experiments will not only extend our understanding of how gonad development is specified, but they will also help to determine at a molecular level how FOXA proteins regulate developmental decisions.
| Yuzyuk, T; Fakhouri, T H I; Kiefer, J et al. (2009) The polycomb complex protein mes-2/E(z) promotes the transition from developmental plasticity to differentiation in C. elegans embryos. Dev Cell 16:699-710 |
| Kiefer, Julie C; Smith, Pliny A; Mango, Susan E (2007) PHA-4/FoxA cooperates with TAM-1/TRIM to regulate cell fate restriction in the C. elegans foregut. Dev Biol 303:611-24 |
