Publications by authors named "Beth A Maguire"

Epigenetic regulatory mechanisms are underappreciated, yet are critical for enteric nervous system (ENS) development and maintenance. We discovered that fetal loss of the epigenetic regulator Bap1 in the ENS lineage caused severe postnatal bowel dysfunction and early death in Tyrosinase-Cre Bap1fl/fl mice. Bap1-depleted ENS appeared normal in neonates; however, by P15, Bap1-deficient enteric neurons were largely absent from the small and large intestine of Tyrosinase-Cre Bap1fl/fl mice.

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Background And Aims: Bowel function requires coordinated activity of diverse enteric neuron subtypes. Our aim was to define gene expression in these neuron subtypes to facilitate development of novel therapeutic approaches to treat devastating enteric neuropathies, and to learn more about enteric nervous system function.

Methods: To identify subtype-specific genes, we performed single-nucleus RNA-seq on adult mouse and human colon myenteric plexus, and single-cell RNA-seq on E17.

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Article Synopsis
  • Researchers discovered that mice missing the DLX1 and DLX2 transcription factors have slower small bowel transit and fewer nerve contractions, indicating bowel motility issues.
  • Despite the lack of visible structural defects in the enteric nervous system, RNA sequencing showed that many genes, particularly vasoactive intestinal peptide (Vip), were dysregulated in these mice.
  • The study establishes a new link between DLX genes and VIP expression, suggesting their absence can lead to serious bowel motility problems, with potential implications for conditions like chronic intestinal pseudo-obstruction (CIPO) syndrome.
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