Characterization of ceh-27/Nkx2.1 in Caenorhabditis elegans Pharyngeal Nervous System Development
Disciplines
Developmental Neuroscience | Genetics | Molecular and Cellular Neuroscience
Abstract (300 words maximum)
Attention Deficit Hyperactivity Disorder (ADHD) is a polygenic hereditary disorder affecting roughly 250 million people worldwide. The ADHD associated gene Nkx2.1 codes for the homeobox transcription factor NKX2-1, which plays a critical role in regulating gene expression by binding to specific DNA sequences and controlling the transcription of target genes. Heterozygous mutations in Nkx2.1 are linked to the development of benign hereditary chorea, which also presents as ADHD in adults. Understanding the gene regulatory environment around Nkx2.1 is critical for characterizing its downstream effects on neurodevelopment and can help identify other genes that contribute to ADHD. Nkx2.1 is highly conserved across phyla, allowing the use of model organisms to better understand Nkx2.1 function. The nematode Caenorhabditis elegans (C. elegans) can be used to study Nkx2.1 through its orthologous homeobox gene ceh-27. C. elegans has an invariant cell lineage, well defined nervous system, and fully mapped genome which makes it ideal for characterizing the role of ceh-27. Our preliminary data suggests that ceh-27 plays a role in neuronal specification and is required for normal pharyngeal development. However, its specific regulatory targets remain unclear. To further investigate ceh-27’s gene regulatory environment and its downstream influence on pharynx development, genetically encoded florescent reporters were crossed into a ceh-27 null mutant allele to highlight different cell types within and around the pharynx. Through the use of confocal time-lapse video microscopy and direct analysis of pharyngeal specific markers, we aim to confirm that ceh-27 has key roles in embryonic pharyngeal nervous system development. Future directions include using single cell RNA sequencing to further characterize ceh-27 transcriptional targets.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Dr. Martin Hudson
Characterization of ceh-27/Nkx2.1 in Caenorhabditis elegans Pharyngeal Nervous System Development
Attention Deficit Hyperactivity Disorder (ADHD) is a polygenic hereditary disorder affecting roughly 250 million people worldwide. The ADHD associated gene Nkx2.1 codes for the homeobox transcription factor NKX2-1, which plays a critical role in regulating gene expression by binding to specific DNA sequences and controlling the transcription of target genes. Heterozygous mutations in Nkx2.1 are linked to the development of benign hereditary chorea, which also presents as ADHD in adults. Understanding the gene regulatory environment around Nkx2.1 is critical for characterizing its downstream effects on neurodevelopment and can help identify other genes that contribute to ADHD. Nkx2.1 is highly conserved across phyla, allowing the use of model organisms to better understand Nkx2.1 function. The nematode Caenorhabditis elegans (C. elegans) can be used to study Nkx2.1 through its orthologous homeobox gene ceh-27. C. elegans has an invariant cell lineage, well defined nervous system, and fully mapped genome which makes it ideal for characterizing the role of ceh-27. Our preliminary data suggests that ceh-27 plays a role in neuronal specification and is required for normal pharyngeal development. However, its specific regulatory targets remain unclear. To further investigate ceh-27’s gene regulatory environment and its downstream influence on pharynx development, genetically encoded florescent reporters were crossed into a ceh-27 null mutant allele to highlight different cell types within and around the pharynx. Through the use of confocal time-lapse video microscopy and direct analysis of pharyngeal specific markers, we aim to confirm that ceh-27 has key roles in embryonic pharyngeal nervous system development. Future directions include using single cell RNA sequencing to further characterize ceh-27 transcriptional targets.