Collaborative Research: RUI: Integration of temporal, positional, and sex-specifying cues in neuronal development

Reproductive behaviors depend on specific neuronal circuits that emerge during development. This investigation will discover the molecules that regulate how specific neurons that control reproductive behaviors are generated by using the worm C. elegans as a model. As genes that control fundamental processes are often similar among diverse organisms, these studies may provide a basis for future investigations that shed light on human reproduction and on nervous system differences and disorders that display a sex bias.

The study is fully integrated in the curricular courses of undergraduate students at Carleton College who will investigate how neurons develop and make connections that allow them to regulate reproduction. Undergraduate course-based and summer research experiences will engage students in answering significant questions in developmental neurobiology, practicing independent thinking, critical analysis, engagement with literature, and effective communication.

This work seeks to elucidate how sex-determining signals are integrated with sex-shared programs of neural development, using the well-understood neuronal development of the nematode C. elegans as a model. In C. elegans, several neuroblasts of the P lineage divide in males, but not in hermaphrodites, initiating divergent programs of differentiation in the ventral cord and tail.

These sex-specific programs depend on the sex determination factor TRA-1 and the Hox proteins MAB-5 and LIN-39. This work investigates the role of TRA-1 and the Hox proteins, as well as seeking previously unknown regulatory components, such as cell cycle regulators and developmental timers. The investigators and their undergraduate students have developed reagents to address how these regulators interact with each other to promote sex-specific nervous system organization.

A cell cycle sensor and a masculinized P lineage strain, P-masc, allow exploration of the mechanisms by which sex-determining factors act within neuronal lineages to influence early neurogenesis as well as differentiation, circuit formation, and behavior. Whereas previous studies of masculinized neurons have focused on later stages of neuronal development and function, this work will identify early events in the organization of the sex-specific nervous system.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.