The Homeobox Gene ceh-27 is Required for C. elegans Embryonic Development
Disciplines
Other Physical Sciences and Mathematics
Abstract (300 words maximum)
Defects in nervous system development have been linked to multiple neurological conditions including autism spectrum disorder. Neurogenins are one of the earliest acting classes of pro-neural transcription factors. Mutations in human neurogenin1 have been associated with autism, strongly implying this gene is in the etiology of this complex polygenic disorder. Defects in neurogenin transcription/translation have the potential to contribute to autism phenotypes, creating an urgency for further study. Neurogenin is deeply conserved across phyla, allowing us to study its function using genetically amenable species such as the nematode Caenorhabditis elegans. Previous studies showed that C. elegans ngn-1/neurogenin is required for multiple aspects of nervous system development and function. However, the transcription factors that control ngn-1 expression have not been characterized.We used publicly available single-cell RNA sequencing data to identify transcription factors that may control cell fate in ngn-1 expressing neuroblasts. We found that the homeobox gene ceh-27 was expressed prior to the onset of ngn-1 expression, making it a candidate ngn-1 “controller”. ceh-27 encodes a homeodomain protein of the NK-2 class and is similar to Drosophila scarecrow and human NKX-2. We found that a deletion mutation in the ceh-27 gene led to 100% lethality, indicating that it is absolutely required for normal embryonic development. 4D time-lapse video microscopy of embryonic development revealed extensive defects during embryonic cell migration. Future work will investigate whether ceh-27 functions in a linear developmental pathway with ngn-1 can control nervous system development and function.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Martin Hudson
The Homeobox Gene ceh-27 is Required for C. elegans Embryonic Development
Defects in nervous system development have been linked to multiple neurological conditions including autism spectrum disorder. Neurogenins are one of the earliest acting classes of pro-neural transcription factors. Mutations in human neurogenin1 have been associated with autism, strongly implying this gene is in the etiology of this complex polygenic disorder. Defects in neurogenin transcription/translation have the potential to contribute to autism phenotypes, creating an urgency for further study. Neurogenin is deeply conserved across phyla, allowing us to study its function using genetically amenable species such as the nematode Caenorhabditis elegans. Previous studies showed that C. elegans ngn-1/neurogenin is required for multiple aspects of nervous system development and function. However, the transcription factors that control ngn-1 expression have not been characterized.We used publicly available single-cell RNA sequencing data to identify transcription factors that may control cell fate in ngn-1 expressing neuroblasts. We found that the homeobox gene ceh-27 was expressed prior to the onset of ngn-1 expression, making it a candidate ngn-1 “controller”. ceh-27 encodes a homeodomain protein of the NK-2 class and is similar to Drosophila scarecrow and human NKX-2. We found that a deletion mutation in the ceh-27 gene led to 100% lethality, indicating that it is absolutely required for normal embryonic development. 4D time-lapse video microscopy of embryonic development revealed extensive defects during embryonic cell migration. Future work will investigate whether ceh-27 functions in a linear developmental pathway with ngn-1 can control nervous system development and function.