Understanding the Role of hlh-14 and ceh-27 in the M4 Motor Neuron in C. elegans

Disciplines

Developmental Biology | Developmental Neuroscience | Genetics

Abstract (300 words maximum)

Attention Deficit Hyperactivity Disorder (ADHD) affects millions worldwide and can shape social interactions, health factors, and overall quality of life. The genetic mechanisms underlying ADHD, however, are not well defined. One gene linked to ADHD, Nkx2.1, plays a key role in neuronal differentiation across mammals. Because these transcriptional networks are deeply conserved, studying Nkx2.1’s ortholog, ceh-27, in C. elegans allows these mechanisms to be examined in a simpler, well-mapped nervous system. The worm’s invariant cell lineage and genetic accessibility make it an ideal model for discovering conserved neurodevelopmental pathways. This study investigates the regulatory relationship between ceh-27 and hlh-14, a basic helix-loop-helix transcription factor that promotes early neurogenesis, in the M4 motor neuron. Using C. elegans strains expressing hlh-14::GFP, fluorescence microscopy will compare hlh-14 expression in wild-type and ceh-27 mutant embryos. Spatial and intensity analyses will determine whether ceh-27 represses or activates hlh-14 during M4 specification. By defining how ceh-27 interacts with hlh-14 in a single, invariant neuron (M4), this research will provide more insight into the transcriptional hierarchies that govern neuronal identity in C. elegans and conserved mechanisms relevant to neurodevelopmental disorders.

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Academic department under which the project should be listed

CSM – Molecular and Cellular Biology

Primary Investigator (PI) Name

Dr. Martin Hudson

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Understanding the Role of hlh-14 and ceh-27 in the M4 Motor Neuron in C. elegans

Attention Deficit Hyperactivity Disorder (ADHD) affects millions worldwide and can shape social interactions, health factors, and overall quality of life. The genetic mechanisms underlying ADHD, however, are not well defined. One gene linked to ADHD, Nkx2.1, plays a key role in neuronal differentiation across mammals. Because these transcriptional networks are deeply conserved, studying Nkx2.1’s ortholog, ceh-27, in C. elegans allows these mechanisms to be examined in a simpler, well-mapped nervous system. The worm’s invariant cell lineage and genetic accessibility make it an ideal model for discovering conserved neurodevelopmental pathways. This study investigates the regulatory relationship between ceh-27 and hlh-14, a basic helix-loop-helix transcription factor that promotes early neurogenesis, in the M4 motor neuron. Using C. elegans strains expressing hlh-14::GFP, fluorescence microscopy will compare hlh-14 expression in wild-type and ceh-27 mutant embryos. Spatial and intensity analyses will determine whether ceh-27 represses or activates hlh-14 during M4 specification. By defining how ceh-27 interacts with hlh-14 in a single, invariant neuron (M4), this research will provide more insight into the transcriptional hierarchies that govern neuronal identity in C. elegans and conserved mechanisms relevant to neurodevelopmental disorders.