While a number of principles underlying cell fate specification have been discovered, the mechanisms that create such vast neuronal diversity are still not well understood. Neural differentiation is often thought of as a two step process, one that establishes general neural fate and a second that further differentiates cell types. This specification can be taken a step further as in bilateral organisms, initially similarly-fated neurons on the right and left sides often acquire different functions. This proposal will study links between these steps of differentiation by analyzing a gene that affects the acquisition of both general and specific cell fates in the Caenorhabditis elegans ASE taste neurons. In a screen for lateral asymmetry defects in the bilaterally symmetric ASE neurons, one surprising mutant affects the neurons' ability to not only acquire left and right fate, but also to acquire ASE fate altogether. It is the first mutant of its kind to be pulled out of a screen in this context. Within this proposal, the mutant will be characterized, mapped and cloned, and functionally dissected. Initial observations suggest that this gene could be involved both in establishing ASE cell fate and in promoting the asymmetric expression of a number of right and left cell fate markers. ? ?
| Sarin, Sumeet; Bertrand, Vincent; Bigelow, Henry et al. (2010) Analysis of multiple ethyl methanesulfonate-mutagenized Caenorhabditis elegans strains by whole-genome sequencing. Genetics 185:417-30 |
| Bigelow, Henry; Doitsidou, Maria; Sarin, Sumeet et al. (2009) MAQGene: software to facilitate C. elegans mutant genome sequence analysis. Nat Methods 6:549 |
| Sarin, Sumeet; Antonio, Celia; Tursun, Baris et al. (2009) The C. elegans Tailless/TLX transcription factor nhr-67 controls neuronal identity and left/right asymmetric fate diversification. Development 136:2933-44 |
| Shen, Yufeng; Sarin, Sumeet; Liu, Ye et al. (2008) Comparing platforms for C. elegans mutant identification using high-throughput whole-genome sequencing. PLoS One 3:e4012 |
| Sarin, Sumeet; Prabhu, Snehit; O'Meara, M Maggie et al. (2008) Caenorhabditis elegans mutant allele identification by whole-genome sequencing. Nat Methods 5:865-7 |
