Disciplines
Cell and Developmental Biology | Cell Biology | Microbiology
Abstract (300 words maximum)
Accurate control of neuronal cell identification and movement is crucial to embryonic development. Defects in this process can lead to neurodevelopmental disorders, creating an imperative for further study. The transcription factor neurogenin is required for multiple neurodevelopmental processes during vertebrate embryonic development and mutations in this gene underpin multiple human neurological disorders. Despite this, little is known about how this gene controls nervous system development and function. Neurogenin is deeply conserved across phyla. As such, we can investigate neurogenin function in simple systems such as the nematode Caenorhabditis elegans, which has a close ortholog of neurogenin, ngn-1. Previous work in the Hudson lab revealed that C. elegans ngn-1 mutants have 45% embryonic lethality. Using time-lapse video microscopy, we found that most ngn-1 mutants die during the “elongation” phase of development when the worm embryo is “squeezing” itself into a worm shape. We find that the primary source of death is via epithelial rupture in the posterior ventral region, close to the ano-rectal junction. We used a marker of epithelial junctions, ajm-1:::GFP, to highlight epithelial cell-cell boundaries during development. We find that ngn-1 mutants have defects in the gut-to-epithelial boundaries at the 1.5 stage of embryonic development. This suggests that ngn-1 is required for the proper specification of the crucial developmental event. Work is on-going to understand why a proneural transcription factor is required for epithelial integrity.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Martin L. Hudson
Included in
The Role of Proneural Transcription Factor ngn-1/neurogenin during Caenorhabditis elegans Embryonic Development
Accurate control of neuronal cell identification and movement is crucial to embryonic development. Defects in this process can lead to neurodevelopmental disorders, creating an imperative for further study. The transcription factor neurogenin is required for multiple neurodevelopmental processes during vertebrate embryonic development and mutations in this gene underpin multiple human neurological disorders. Despite this, little is known about how this gene controls nervous system development and function. Neurogenin is deeply conserved across phyla. As such, we can investigate neurogenin function in simple systems such as the nematode Caenorhabditis elegans, which has a close ortholog of neurogenin, ngn-1. Previous work in the Hudson lab revealed that C. elegans ngn-1 mutants have 45% embryonic lethality. Using time-lapse video microscopy, we found that most ngn-1 mutants die during the “elongation” phase of development when the worm embryo is “squeezing” itself into a worm shape. We find that the primary source of death is via epithelial rupture in the posterior ventral region, close to the ano-rectal junction. We used a marker of epithelial junctions, ajm-1:::GFP, to highlight epithelial cell-cell boundaries during development. We find that ngn-1 mutants have defects in the gut-to-epithelial boundaries at the 1.5 stage of embryonic development. This suggests that ngn-1 is required for the proper specification of the crucial developmental event. Work is on-going to understand why a proneural transcription factor is required for epithelial integrity.