Feedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis.

Muscle precursor cells known as myoblasts are essential for muscle development and regeneration. Notch signaling is an ancient intercellular communication mechanism that plays prominent roles in controlling the myogenic program of myoblasts. Currently whether and how the myogenic cues feedback to re...

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Autores principales: Haifeng Zhang, Renjie Shang, Pengpeng Bi
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Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2021
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Acceso en línea:https://doaj.org/article/1afa77cfdce446979f30150a4bc33693
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spelling oai:doaj.org-article:1afa77cfdce446979f30150a4bc336932021-12-02T20:02:53ZFeedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis.1553-73901553-740410.1371/journal.pgen.1009729https://doaj.org/article/1afa77cfdce446979f30150a4bc336932021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009729https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Muscle precursor cells known as myoblasts are essential for muscle development and regeneration. Notch signaling is an ancient intercellular communication mechanism that plays prominent roles in controlling the myogenic program of myoblasts. Currently whether and how the myogenic cues feedback to refine Notch activities in these cells are largely unknown. Here, by mouse and human gene gain/loss-of-function studies, we report that MyoD directly turns on the expression of Notch-ligand gene Dll1 which activates Notch pathway to prevent precautious differentiation in neighboring myoblasts, while autonomously inhibits Notch to facilitate a myogenic program in Dll1 expressing cells. Mechanistically, we studied cis-regulatory DNA motifs underlying the MyoD-Dll1-Notch axis in vivo by characterizing myogenesis of a novel E-box deficient mouse model, as well as in human cells through CRISPR-mediated interference. These results uncovered the crucial transcriptional mechanism that mediates the reciprocal controls of Notch and myogenesis.Haifeng ZhangRenjie ShangPengpeng BiPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 8, p e1009729 (2021)
institution DOAJ
collection DOAJ
language EN
topic Genetics
QH426-470
spellingShingle Genetics
QH426-470
Haifeng Zhang
Renjie Shang
Pengpeng Bi
Feedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis.
description Muscle precursor cells known as myoblasts are essential for muscle development and regeneration. Notch signaling is an ancient intercellular communication mechanism that plays prominent roles in controlling the myogenic program of myoblasts. Currently whether and how the myogenic cues feedback to refine Notch activities in these cells are largely unknown. Here, by mouse and human gene gain/loss-of-function studies, we report that MyoD directly turns on the expression of Notch-ligand gene Dll1 which activates Notch pathway to prevent precautious differentiation in neighboring myoblasts, while autonomously inhibits Notch to facilitate a myogenic program in Dll1 expressing cells. Mechanistically, we studied cis-regulatory DNA motifs underlying the MyoD-Dll1-Notch axis in vivo by characterizing myogenesis of a novel E-box deficient mouse model, as well as in human cells through CRISPR-mediated interference. These results uncovered the crucial transcriptional mechanism that mediates the reciprocal controls of Notch and myogenesis.
format article
author Haifeng Zhang
Renjie Shang
Pengpeng Bi
author_facet Haifeng Zhang
Renjie Shang
Pengpeng Bi
author_sort Haifeng Zhang
title Feedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis.
title_short Feedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis.
title_full Feedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis.
title_fullStr Feedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis.
title_full_unstemmed Feedback regulation of Notch signaling and myogenesis connected by MyoD-Dll1 axis.
title_sort feedback regulation of notch signaling and myogenesis connected by myod-dll1 axis.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/1afa77cfdce446979f30150a4bc33693
work_keys_str_mv AT haifengzhang feedbackregulationofnotchsignalingandmyogenesisconnectedbymyoddll1axis
AT renjieshang feedbackregulationofnotchsignalingandmyogenesisconnectedbymyoddll1axis
AT pengpengbi feedbackregulationofnotchsignalingandmyogenesisconnectedbymyoddll1axis
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