Gene regulatory factors that control the identities of specific neuron types in Caenorhabditis elegans.

摘要

The nervous system is the most complex and diverse system of the human body. And so it is in the round worm Caenorhabditis elegans. The easy manipulation, maintenance and visualization features of the worm have made it one of the most understood metazoans for linking genetics, anatomy, development and behavior. This thesis work focuses on two aspects during neural development in C. elegans: neuronal asymmetry in the ASEL/R gustatory neurons and terminal fate determination of the AIA interneuron as well as the NSM neurosecretory motor neuron. I have cloned and characterized LSY-27, a C2H2 zinc finger transcription factor, which is essential in assisting the onset of the LIM homeodomain transcription factor lim-6 to repress ASER expressed genes in ASEL. I have also took part in characterizing LSY-12, a MYST family histone acetyltransferase, and LSY-13, a previously uncharacterized PHD finger protein, which cooperate with the bromodomain containing protein LIN-49 and form the MYST complex to both initiate and maintain the ASEL fate. I have also studied the fate determination of several distinct neuronal cell types. I dissected the cis-regulatory information of AIA expressed genes and identified that the LIM homeodomain transcription factor TTX-3 is required for AIA fate, possibly together with another yet unknown transcription factor. TTX-3 also acts synergistically with the POU-domain transcription factor UNC-86 as master regulators for NSM. TTX-3 may also act as the terminal selector for ASK. This work provides extra evidence for the terminal selector concept and further demonstrates that individual neurons use unique and combinatorial codes of transcription factors to achieve their terminal identities, and that the same regulatory factor can be reused as a terminal selector in distinct cell types through cooperation with different cofactors.