Disciplines
Cell and Developmental Biology
Abstract (300 words maximum)
When the development of an organism’s nervous system is interrupted or altered, it can significantly impact that organism’s ability to survive and function properly. In our lab, we use a species of nematode called Caenorhabditis elegans as a model organism to characterize the roles of important transcription factors in human neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). Utilizing C. elegans makes analyzing this process in a lab very easy for many reasons; they are very small, have a rapid life cycle, invariant cell lineage, transparent bodies, and most importantly, around 80% of their genes have human orthologs. In C. elegans, ceh-27, which is orthologous to human NKX2-1, acts as a homeobox (master controller) gene. Previous research in the Hudson lab revealed that ceh-27 is necessary for normal embryogenesis. In ceh-27 mutants, the AIY interneurons and SMDD motor neurons do not develop correctly, leading to embryo fatality. This indicates that ceh-27 controls the normal development of these cells. In humans, mutations in the NKX2-1 gene can lead to the development of ADHD, characterized by hyperactivity and impulsivity. To better understand the role of ceh-27 in embryonic development, we set out to rescue this mutation. To do this, we injected wild type animals with ceh-27 genomic DNA (marked with coelomocyte RFP) then crossed that transgene into ceh-27 mutants, balanced with the tmC12 balancer chromosome. Work is on-going to determine if the transgene will rescue AIY neuron development in embryos. Once we better understand the role that ceh-27 has in neuron development, we can then apply this to our knowledge of its human homolog’s role in neural development.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Martin Hudson
Included in
Can a ceh-27/Nkx2.1 transgene rescue ceh-27 neurodevelopmental defects?
When the development of an organism’s nervous system is interrupted or altered, it can significantly impact that organism’s ability to survive and function properly. In our lab, we use a species of nematode called Caenorhabditis elegans as a model organism to characterize the roles of important transcription factors in human neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). Utilizing C. elegans makes analyzing this process in a lab very easy for many reasons; they are very small, have a rapid life cycle, invariant cell lineage, transparent bodies, and most importantly, around 80% of their genes have human orthologs. In C. elegans, ceh-27, which is orthologous to human NKX2-1, acts as a homeobox (master controller) gene. Previous research in the Hudson lab revealed that ceh-27 is necessary for normal embryogenesis. In ceh-27 mutants, the AIY interneurons and SMDD motor neurons do not develop correctly, leading to embryo fatality. This indicates that ceh-27 controls the normal development of these cells. In humans, mutations in the NKX2-1 gene can lead to the development of ADHD, characterized by hyperactivity and impulsivity. To better understand the role of ceh-27 in embryonic development, we set out to rescue this mutation. To do this, we injected wild type animals with ceh-27 genomic DNA (marked with coelomocyte RFP) then crossed that transgene into ceh-27 mutants, balanced with the tmC12 balancer chromosome. Work is on-going to determine if the transgene will rescue AIY neuron development in embryos. Once we better understand the role that ceh-27 has in neuron development, we can then apply this to our knowledge of its human homolog’s role in neural development.