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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2021
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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) |
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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 |
_version_ |
1718375645998743552 |