Project Title

Identification of ngn-1/Neurogenin Transcriptional Controllers

Academic department under which the project should be listed

Molecular & Cellular Biology

Faculty Sponsor Name

Martin Hudson

no human subject

Project Type

Event

Abstract (300 words maximum)

Transcription factors are a class of proteins that specify when and where genes are transcribed. The transcription factor neurogenin is required for multiple neurodevelopmental processes during vertebrate embryonic development and mutations in this gene are implicated in a variety of human neurological disorders. Despite this, little is known about how this gene functions. Neurogenin is deeply conserved across phyla. As such, we can investigate neurogenin in simple organisms such as the nematode Caenorhabditis elegans, which has a close ortholog of neurogenin, ngn-1. Previous work in the Hudson lab revealed that ngn-1 controls the expression of eight downstream transcription factors. However, the genes that control ngn-1 itself are not known. This project aims to identify and validate ngn-1 transcriptional controllers.

We previously used the RNAseq dataset published by Packer et al. (Science, 2019) to identify transcription factors expressed in the “parent” cells of ngn-1 expressing cells. We hypothesize that these genes are required for ngn-1 transcription. This suggests that loss-of-function mutations in a gene required for ngn-1 transcription may show a similar phenotype to an ngn-1 loss-of-function mutation (embryonic lethality, axon guidance defects, cell fate specification defects, etc.)

Unsurprisingly, many of the genes identified as candidate ngn-1 transcriptional controllers show lethal phenotypes. To validate our approach, we will need to design genetic crossing protocols to handle these lethal alleles and to cross appropriate reporter genes into these loss-of-function backgrounds to validate our hypothesis. This presentation will summarize our experimental designs, along with our preliminary results.

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Identification of ngn-1/Neurogenin Transcriptional Controllers

Transcription factors are a class of proteins that specify when and where genes are transcribed. The transcription factor neurogenin is required for multiple neurodevelopmental processes during vertebrate embryonic development and mutations in this gene are implicated in a variety of human neurological disorders. Despite this, little is known about how this gene functions. Neurogenin is deeply conserved across phyla. As such, we can investigate neurogenin in simple organisms such as the nematode Caenorhabditis elegans, which has a close ortholog of neurogenin, ngn-1. Previous work in the Hudson lab revealed that ngn-1 controls the expression of eight downstream transcription factors. However, the genes that control ngn-1 itself are not known. This project aims to identify and validate ngn-1 transcriptional controllers.

We previously used the RNAseq dataset published by Packer et al. (Science, 2019) to identify transcription factors expressed in the “parent” cells of ngn-1 expressing cells. We hypothesize that these genes are required for ngn-1 transcription. This suggests that loss-of-function mutations in a gene required for ngn-1 transcription may show a similar phenotype to an ngn-1 loss-of-function mutation (embryonic lethality, axon guidance defects, cell fate specification defects, etc.)

Unsurprisingly, many of the genes identified as candidate ngn-1 transcriptional controllers show lethal phenotypes. To validate our approach, we will need to design genetic crossing protocols to handle these lethal alleles and to cross appropriate reporter genes into these loss-of-function backgrounds to validate our hypothesis. This presentation will summarize our experimental designs, along with our preliminary results.