The Role of Homeobox Transcription Factor ceh-27/Nkx2.1 in Nervous System Development
Disciplines
Developmental Neuroscience | Genetics | Molecular and Cellular Neuroscience
Abstract (300 words maximum)
Transcription factors are proteins that activate or repress gene expression. Nkx2.1 and neurogenin are both transcription factors required for normal neural development and function. Mutations in these genes have been associated with autism and attention deficit/hyperactivity disorder, prompting a need for further research to understand the transcriptional regulation of these genes and their functions in nervous system development. Both genes are strongly conserved across phyla, which allows us to examine Nkx2.1 and neurogenin function using genetics approaches in a simple invertebrate system such as the nematode Caenorhabditis elegans. The C. elegans orthologs of Nkx2.1 and neurogenin are ceh-27 and ngn-1, respectively. The purpose of this project is to use C. elegans to investigate if ceh-27/Nkx2.1 controls ngn-1/neurogenin gene expression to specify AIY interneuron cell fate. 4D time-lapse microscopy revealed that embryonic expression of ngn-1 is downregulated in four midbody cells in embryos containing a homozygous ceh-27 deletion allele. These four cells, the AIYL/R and SMDDL/R neurons, express ngn-1 in wildtype organisms and fail to express ngn-1 in homozygous mutants, indicating that ceh-27 is required for ngn-1 expression in these cells. Future work will investigate the transcriptional regulation of ceh-27 during embryonic development and identify other downstream targets under ceh-27 transcriptional control.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Martin L. Hudson
The Role of Homeobox Transcription Factor ceh-27/Nkx2.1 in Nervous System Development
Transcription factors are proteins that activate or repress gene expression. Nkx2.1 and neurogenin are both transcription factors required for normal neural development and function. Mutations in these genes have been associated with autism and attention deficit/hyperactivity disorder, prompting a need for further research to understand the transcriptional regulation of these genes and their functions in nervous system development. Both genes are strongly conserved across phyla, which allows us to examine Nkx2.1 and neurogenin function using genetics approaches in a simple invertebrate system such as the nematode Caenorhabditis elegans. The C. elegans orthologs of Nkx2.1 and neurogenin are ceh-27 and ngn-1, respectively. The purpose of this project is to use C. elegans to investigate if ceh-27/Nkx2.1 controls ngn-1/neurogenin gene expression to specify AIY interneuron cell fate. 4D time-lapse microscopy revealed that embryonic expression of ngn-1 is downregulated in four midbody cells in embryos containing a homozygous ceh-27 deletion allele. These four cells, the AIYL/R and SMDDL/R neurons, express ngn-1 in wildtype organisms and fail to express ngn-1 in homozygous mutants, indicating that ceh-27 is required for ngn-1 expression in these cells. Future work will investigate the transcriptional regulation of ceh-27 during embryonic development and identify other downstream targets under ceh-27 transcriptional control.