Characterizing the Regulatory Environment of the 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 regulatory proteins that can activate or repress gene expression by interacting with DNA sequences. Nkx2.1 is a homeodomain transcription factor in humans that is responsible for normal nervous system formation and function. Heterozygous mutations in this gene have been associated with attention deficit/hyperactivity disorder indicating a need for further study to better understand the transcriptional regulation of this gene and its role in neural development. Nkx2.1 is strongly conserved across phyla, allowing us to examine its regulatory environment in a simple model organism, such as the nematode Caenorhabditis elegans. The well characterized genome, invariant cell lineage, and simple nervous system, and the availability of powerful genetic tools, make C. elegans ideal for fundamental studies on the brain and its development. The C. elegans ortholog of Nkx2.1, called ceh-27, is a homeodomain transcription factor that is absolutely required for embryonic development and the formation of the AIYL/R interneurons. A key feature of homeodomain proteins is their DNA-binding site, and many have been identified as regulating their own transcription. The purpose of this project is to determine if ceh-27 is transcriptionally autoregulated in order to better understand the regulatory mechanisms controlling Nkx2.1 expression in humans. Data collected from 4-D timelapse microscopy assays indicate that ceh-27 works to repress its own transcription; animals with a homozygous ceh-27 mutation exhibit increased ceh-27 transcriptional activity compared to wild type organisms. Future work will identify ceh-27 autoregulatory elements along with downstream genes under the transcriptional control of ceh-27.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Martin L. Hudson
Characterizing the Regulatory Environment of the Homeobox Transcription Factor ceh-27/Nkx2.1 in Nervous System Development
Transcription factors are regulatory proteins that can activate or repress gene expression by interacting with DNA sequences. Nkx2.1 is a homeodomain transcription factor in humans that is responsible for normal nervous system formation and function. Heterozygous mutations in this gene have been associated with attention deficit/hyperactivity disorder indicating a need for further study to better understand the transcriptional regulation of this gene and its role in neural development. Nkx2.1 is strongly conserved across phyla, allowing us to examine its regulatory environment in a simple model organism, such as the nematode Caenorhabditis elegans. The well characterized genome, invariant cell lineage, and simple nervous system, and the availability of powerful genetic tools, make C. elegans ideal for fundamental studies on the brain and its development. The C. elegans ortholog of Nkx2.1, called ceh-27, is a homeodomain transcription factor that is absolutely required for embryonic development and the formation of the AIYL/R interneurons. A key feature of homeodomain proteins is their DNA-binding site, and many have been identified as regulating their own transcription. The purpose of this project is to determine if ceh-27 is transcriptionally autoregulated in order to better understand the regulatory mechanisms controlling Nkx2.1 expression in humans. Data collected from 4-D timelapse microscopy assays indicate that ceh-27 works to repress its own transcription; animals with a homozygous ceh-27 mutation exhibit increased ceh-27 transcriptional activity compared to wild type organisms. Future work will identify ceh-27 autoregulatory elements along with downstream genes under the transcriptional control of ceh-27.