Molecular and Cellular Mechanisms of Olfactory Neuron Specification in C. elegans

Neuronal diversity is crucial in the nervous system, which gives us the ability to respond to the environment, express emotions, and form ideas. One mechanism to achieve neuronal diversity is through neuronal asymmetry across the left-right axis of the brain. The stagging complexity poses challenges for us to study the molecular and cellular mechanisms underlying neuronal asymmetry differentiation. Many aspects related to neuronal asymmetry remain to be elucidated. Caenorhabditis elegans as a model system has been proven to be a powerful tool to address complex problems in neuronal development. This thesis presents two mechanisms in the establishment of asymmetry differentiation in the pair of AWC olfactory neurons in C. elegans. After general AWC identity is determined, they are specified into two functionally distinct subtypes AWCOFF and AWCON through a series of stochastic and coordinated events. The HMX/NKX transcription factor MLS-2 and a homothorax/Meis/TALE homeodomain protein UNC-62 specify the general AWC identity during early embryogenesis. Then in late embryogenesis, they function cell autonomously to promote the AWCON subtype. A mutation in apical junction molecule ajm-1 was identified from a non-biased forward genetic screen for the modifier of SLO BK potassium channel. It is sufficient and required to function in non-neuronal cells such as hypodermal and glial cells to regulate AWC asymmetry, possibly via its regulation on a mechanosensitive ion channel. Mechanisms described here may be conserved in mammalian systems and shed light on further understanding of neuronal diversity.