Scholarlink

<p>Biallelic mutations in multiple EGF domain protein 10 (<i>MEGF10</i>) gene cause EMARDD (early myopathy, areflexia, respiratory distress and dysphagia) in humans, a severe recessive myopathy, associated with reduced numbers of PAX7 positive satellite cells. To better understand the role of MEGF10 in satellite cells, we overexpressed human MEGF10 in mouse <i>H-2k</i><sup><i>b</i></sup>-tsA58 myoblasts and found that it inhibited fusion. Addition of purified extracellular domains of human MEGF10, with (ECD) or without (EGF) the N-terminal EMI domain to <i>H-2k</i><sup><i>b</i></sup>-tsA58 myoblasts, showed that the ECD was more effective at reducing myoblast adhesion and fusion by day 7 of differentiation, yet promoted adhesion of myoblasts to non-adhesive surfaces, highlighting the importance of the EMI domain in these behaviours. We additionally tested the role of Megf10 in vivo using transgenic mice with reduced (<i>Megf10</i><sup>+/−</sup>) or no (<i>Megf10</i><sup>−/−</sup>) Megf10. We found that the extensor digitorum longus muscle had fewer anti-Pax7 stained cell nuclei and was less able to undergo hypertrophy in response to muscle overload concomitant with a lower level of satellite cell activation. Taken together, our data suggest that MEGF10 may promote satellite cell adhesion and survival and prevent premature fusion helping to explain its role in EMARDD.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The role of MEGF10 in myoblast fusion and hypertrophic response to overload of skeletal muscle

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月18日

查看全文
  • Louise Richardson,
  • Ruth Hughes,
  • Colin A. Johnson,
  • Stuart Egginton,
  • Michelle Peckham

摘要

Biallelic mutations in multiple EGF domain protein 10 (MEGF10) gene cause EMARDD (early myopathy, areflexia, respiratory distress and dysphagia) in humans, a severe recessive myopathy, associated with reduced numbers of PAX7 positive satellite cells. To better understand the role of MEGF10 in satellite cells, we overexpressed human MEGF10 in mouse H-2kb-tsA58 myoblasts and found that it inhibited fusion. Addition of purified extracellular domains of human MEGF10, with (ECD) or without (EGF) the N-terminal EMI domain to H-2kb-tsA58 myoblasts, showed that the ECD was more effective at reducing myoblast adhesion and fusion by day 7 of differentiation, yet promoted adhesion of myoblasts to non-adhesive surfaces, highlighting the importance of the EMI domain in these behaviours. We additionally tested the role of Megf10 in vivo using transgenic mice with reduced (Megf10+/−) or no (Megf10−/−) Megf10. We found that the extensor digitorum longus muscle had fewer anti-Pax7 stained cell nuclei and was less able to undergo hypertrophy in response to muscle overload concomitant with a lower level of satellite cell activation. Taken together, our data suggest that MEGF10 may promote satellite cell adhesion and survival and prevent premature fusion helping to explain its role in EMARDD.