Morphological and molecular characterization of somatosensory neurogenesis

Abstract

Organisms across phylogeny have neuronal circuits that control everyday activities. The somatosensory network, for example, is specifically utilized to sense the external environment and is important to properly inform the animal on its surroundings. The information encoded in this sensory circuit allows an animal to distinguish painful strikes from gentle brushes and thereby is essential for animal survival. My work establishes C. elegans as a model for studying the generation of pain-sensing cells known as nociceptive neurons that typically have large non-overlapping dendritic arrays that innervate the skin. The C. elegans nociceptive neuron, PVD, is generated through a dynamic error-correction mechanism. This work describes the transcriptional profile of the PVD neuron and identifies multiple transcription factors that are required for the mature dendritic array. I further identify a transcription factor cascade that is required to generate the proper balance of somatosensory neuronal types in C. elegans. We show that MEC-3, AHR-1, and ZAG-1 define a transcriptional code that generates specific somatosensory neurons. Together these proteins define the modality and dendritic architecture of somatosensory neurons. Lastly, I show that the non-overlapping array of PVD is generated through a mechanism known as self-avoidance. I demonstrate that self-avoidance uses a contact-induced retraction event that requires UNC-6/Netrin signaling and actin polymerization. Interestingly, the UNC-6/Netrin pathway is also utilized earlier in development to generate the PVD asymmetric dendritic array. The two functions of UNC-6/Netrin, however, are temporally and modularly different. Together my work provides foundation for studying nociceptive neuron development.