A TALE OF TWO BOWELS: LOSS OF Baz1b AND miR-137 DURING ENTERIC NERVOUS SYSTEM DEVELOPMENT

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Doctor of Philosophy (PhD)
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Cell and Molecular Biology
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Biology
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2023
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Pai, Christopher
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Abstract

The enteric nervous system (ENS) is a network of neurons and glia in the bowel that is essential for survival. Its development is a highly-coordinated dance of many genes and environmental factors as it transitions from neural ectoderm, to neural crest, to enteric neural crest–derived cells (ENCDCs), to a maturing ENS. This dissertation collects two studies into the role of genetic factors in mouse ENS development: Baz1b, a widely-expressed transcription factor that is lost in Williams syndrome, and miR-137, a microRNA that is highly expressed in ENCDCs and regulates a number of genes that have been shown to play a role in ENS development. I show that near-total loss of Baz1b results in high mortality shortly after birth, while partial loss of Baz1b increases the rate of bowel dilation. Despite this, there is no apparent effect on bowel anatomy or function after losing Baz1b. Meanwhile, miR-137 is highly-specific to ENCDCs in the developing mouse bowel, and has been reported to influence neuronal differentiation in the central nervous system. Loss of miR-137 is also reported to cause mortality during mid- to late adolescence, a common phenotype in mouse models of ENS development failure. However, my experiments suggest miR-137 is dispensable during ENS development, contradicting prior reports. I finish by summarizing a few experiments I began but failed to conclude in a satisfying manner, in the hopes that future investigators may find something of use in their research.

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Heuckeroth, Robert, O
Date of degree
2023
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