Dll4 and PDGF-BB Convert Committed Skeletal Myoblasts to Pericytes without Erasing Their Myogenic Memory

Ornella Cappellari, Sara Benedetti, Anna Innocenzi, Francesco Saverio Tedesco, Artal Moreno-Fortuny, Gonzalo Ugarte, Maria Grazia Lampugnani, Graziella Messina, Giulio Cossu

Research output: Contribution to journalArticle

Abstract

Pericytes are endothelial-associated cells that contribute to vessel wall. Here, we report that pericytes may derive from direct conversion of committed skeletal myoblasts. When exposed to Dll4 and PDGF-BB, but not Dll1, skeletal myoblasts downregulate myogenic genes, except Myf5, and upregulate pericyte markers, whereas inhibition of Notch signaling restores myogenesis. Moreover, when cocultured with endothelial cells, skeletal myoblasts, previously treated with Dll4 and PDGF-BB, adopt a perithelial position stabilizing newly formed vessel-like networks in vitro and in vivo. In a transgenic mouse model in which cells expressing MyoD activate Notch, skeletal myogenesis is abolished and pericyte genes are activated. Even if overexpressed, Myf5 does not trigger myogenesis because Notch induces Id3, partially sequestering Myf5 and inhibiting MEF2 expression. Myf5-expressing cells adopt a perithelial position, as occasionally also observed in wild-type (WT) embryos. These data indicate that endothelium, via Dll4 and PDGF-BB, induces a fate switch in adjacent skeletal myoblasts.

Original languageEnglish
Pages (from-to)586-599
Number of pages14
JournalDevelopmental Cell
Volume24
Issue number6
DOIs
Publication statusPublished - Mar 25 2013

ASJC Scopus subject areas

  • Developmental Biology

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    Cappellari, O., Benedetti, S., Innocenzi, A., Tedesco, F. S., Moreno-Fortuny, A., Ugarte, G., Lampugnani, M. G., Messina, G., & Cossu, G. (2013). Dll4 and PDGF-BB Convert Committed Skeletal Myoblasts to Pericytes without Erasing Their Myogenic Memory. Developmental Cell, 24(6), 586-599. https://doi.org/10.1016/j.devcel.2013.01.022