Pcgf1 gene disruption reveals primary involvement of epigenetic mechanism in neuronal subtype specification in the enteric nervous system.

Publisher: Blackwell Publishing on behalf of the Japanese Society of Developmental Biologists Country of Publication: Japan NLM ID: 0356504 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-169X (Electronic) Linking ISSN: 00121592 NLM ISO Abbreviation: Dev Growth Differ Subsets: MEDLINE

Publication: Tokyo : Blackwell Publishing on behalf of the Japanese Society of Developmental Biologists
Original Publication: Nagoya, Japanese Society of Developmental Biologists.

Neurons* ; Enteric Nervous System*/metabolism; Animals ; Mice ; Cell Differentiation/genetics ; Transcription Factors/metabolism ; Epigenesis, Genetic ; Polycomb Repressive Complex 1/genetics ; Polycomb Repressive Complex 1/metabolism

The enteric nervous system (ENS) regulates gut functions independently from the central nervous system (CNS) by its highly autonomic neural circuit that integrates diverse neuronal subtypes. Although several transcription factors are shown to be necessary for the generation of some enteric neuron subtypes, the mechanisms underlying neuronal subtype specification in the ENS remain elusive. In this study, we examined the biological function of Polycomb group RING finger protein 1 (PCGF1), one of the epigenetic modifiers, in the development and differentiation of the ENS by disrupting the Pcgf1 gene selectively in the autonomic-lineage cells. Although ENS precursor migration and enteric neurogenesis were largely unaffected, neuronal differentiation was impaired in the Pcgf1-deficient mice, with the numbers of neurons expressing somatostatin (Sst ⁺ ) decreased in multiple gut regions. Notably, the decrease in Sst ⁺ neurons was associated with the corresponding increase in calbindin ⁺ neurons in the proximal colon. These findings suggest that neuronal subtype conversion may occur in the absence of PCGF1, and that epigenetic mechanism is primarily involved in specification of some enteric neuron subtypes.
(© 2023 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.)

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JPMJCR2021 Core Research for Evolutional Science and Technology; JP22K20740 Japan Society for the Promotion of Science; L23521 Japan Society for the Promotion of Science

Keywords: PCGF1; enteric nervous system; epigenetic mechanism; neuronal subtype conversion; neuronal subtype specification

0 (Transcription Factors)
0 (Pcgf1 protein, mouse)
EC 2.3.2.27 (Polycomb Repressive Complex 1)

Date Created: 20230715 Date Completed: 20231027 Latest Revision: 20241031

20250114

PMC11520948

10.1111/dgd.12880

37452641