2026 Theses Doctoral

A Tale of Two Nematodes: Evolution of Neuronal Fate Specification

Ramadan, Yasmin H.

Although we have made progress in identifying gross differences between nervous system function and organization across species, what remains to be discovered is whether there are conserved molecular factors that drive these evolutionary changes.

We aim to answer this question by comparing cell fate specification in the nervous systems of two distantly related nematode species, Caenorhabditis elegans and Pristionchus pacificus. Using CRISPR, we have engineered null mutations in a series of transcription factors that have been well-characterized as terminal selectors, or master regulators of neuronal fate in C. elegans. These include unc-86, unc-42, unc-3, and unc-30, which have all been shown to regulate the identity of neurons important for locomotion and sensation in C. elegans.

Using RNA-FISH HCR, we molecularly characterize, for the first time, the expression and function of these neuronal identity regulators. Most of the P. pacificus orthologs of these genes show conservation of their roles in nematode behavior, namely locomotion and sensation of mechanosensory or nociceptive cues. Others, like unc-30, show divergence in their terminal selector roles. Together, these comparative analyses allow us to not only characterize neuronal fate specification in a new model organism, but also investigate how these gene regulatory networks are conserved across evolutionary time.