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Decoding neuronal fate specification in the pharynx of Caenorhabditis elegansGulez, Burcu January 2025 (has links)
Santiago Ramon y Cajal’s lifelong pursuit of understanding the intricate cell types in the nervous system ignited a pivotal inquiry in neurobiology. Despite advancements, the fundamental question persists: How does the human brain generate its diverse neuronal cell types? While progress has been made, the mechanisms governing neuronal diversity during brain development remain elusive. Numerous transcription factors and their regulatory mechanisms await elucidation, posing a formidable challenge due to the complexity of the task.
The nematode Caenorhabditis elegans serves as an ideal model organism for investigating neuronal fate specification, owing to its small size, rapid generation time, transparency, and well-annotated genome. This dissertation focuses on the pharyngeal nervous system of C. elegans, comprised of only 20 neurons delineated into 14 distinct types. This simplicity enables detailed analyses of neuronal specifications within a largely autonomous circuit.
This study employs two main approaches: a candidate gene analysis and an unbiased forward genetic screen. Through expression analysis in the laboratory, several homeodomain transcription factors were identified in pharyngeal neurons. Subsequent mutant analysis of these candidate genes tested their roles in specifying the pharyngeal nervous system.
Additionally, this research explored the shifts in homeotic identity between pharyngeal neurons governed by these transcription factors. The forward genetic screen led to the discovery that the chd-7 chromatin regulatory factor plays an essential role in regulating I2 neuronal identity. These insights deepen our understanding of neuronal fate specification and suggest broader implications for understanding complex neural systems.
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