Can a ceh-27 transgene rescue neurodevelopmental defects?
Disciplines
Biology | Cell and Developmental Biology | Genetics and Genomics
Abstract (300 words maximum)
Disruptions to nervous system development and function can be severely detrimental to organismal survival. The nematode Caenorhabditis elegans is an ideal model to study these processes due to their simplicity, and well characterized genome. Since they are transparent, we can use genetically encoded reporter genes to aid in observing their cell fate and neuronal morphology. C. elegans also have an invariant cell lineage which enables precise identification and tracking of individual cells for developmental investigation at the cellular level. In this study, we focused on the gene ceh-27, a C. elegans homolog of the human gene Nkx2.1. In humans, heterozygous mutations in Nkx2.1 lead to attention deficit hyperactivity disorder, in addition to other congenital defects. Previous work in the Hudson lab identified ceh-27 as a master regulatory gene for embryonic development, in addition to being essential for development of the AlY interneurons. Homozygous mutants of ceh-27 exhibit embryonic lethality. To better characterize this gene, we reintroduced ceh-27 genomic DNA marked with coelomocyte RFP into wildtype worms, then crossed this transgene into ceh-27(ok1655) mutants, balanced with the tmC12 balancer chromosome. We also introduced an AIY-specific transgene into this mutant background to determine whether the reintroduction of ceh-27 is sufficient to rescue AlY interneuron fate. Our ultimate goal is to gain a deeper understanding about the way that ceh-27/Nkx2.1 affects C. elegans nervous system development and how these processes are conserved in humans.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Martin Hudson
Can a ceh-27 transgene rescue neurodevelopmental defects?
Disruptions to nervous system development and function can be severely detrimental to organismal survival. The nematode Caenorhabditis elegans is an ideal model to study these processes due to their simplicity, and well characterized genome. Since they are transparent, we can use genetically encoded reporter genes to aid in observing their cell fate and neuronal morphology. C. elegans also have an invariant cell lineage which enables precise identification and tracking of individual cells for developmental investigation at the cellular level. In this study, we focused on the gene ceh-27, a C. elegans homolog of the human gene Nkx2.1. In humans, heterozygous mutations in Nkx2.1 lead to attention deficit hyperactivity disorder, in addition to other congenital defects. Previous work in the Hudson lab identified ceh-27 as a master regulatory gene for embryonic development, in addition to being essential for development of the AlY interneurons. Homozygous mutants of ceh-27 exhibit embryonic lethality. To better characterize this gene, we reintroduced ceh-27 genomic DNA marked with coelomocyte RFP into wildtype worms, then crossed this transgene into ceh-27(ok1655) mutants, balanced with the tmC12 balancer chromosome. We also introduced an AIY-specific transgene into this mutant background to determine whether the reintroduction of ceh-27 is sufficient to rescue AlY interneuron fate. Our ultimate goal is to gain a deeper understanding about the way that ceh-27/Nkx2.1 affects C. elegans nervous system development and how these processes are conserved in humans.