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 DII4 and PDGF-BB, but not DII1, 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 DII4 and PDGF-BB, adopt a perithelial position stabilizing newly formed vessellike 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 DII4 and PDGF-BB, induces a fate switch in adjacent skeletal myoblasts.
Dll4 and PDGF-BB convert committed skeletal myoblasts to pericytes without erasing their myogenic memory / O. Cappellari, S. Benedetti, A. Innocenzi, F.S. Tedesco, A. Moreno-Fortuny, G. Ugarte, M.G. Lampugnani, G. Messina, G. Cossu. - In: DEVELOPMENTAL CELL. - ISSN 1534-5807. - 24:6(2013 Mar 25), pp. 586-599.
|Titolo:||Dll4 and PDGF-BB convert committed skeletal myoblasts to pericytes without erasing their myogenic memory|
MESSINA, GRAZIELLA (Penultimo)
COSSU, GIULIO (Ultimo)
|Parole Chiave:||muscle development; animals; calcium-binding proteins; cells, cultured; coculture techniques; endothelial cells; gene expression regulation, developmental; human umbilical vein endothelial cells; humans; inhibitor of differentiation proteins; intercellular signaling peptides and proteins; intracellular signaling peptides and proteins; membrane proteins; mice; mice, transgenic; muscle, skeletal; myod protein; myoblasts; myoblasts, skeletal; myogenic regulatory factor 5; myogenic regulatory factors; paired box transcription factors; pericytes; proto-oncogene proteins c-sis; signal transduction; transcriptional activation|
|Settore Scientifico Disciplinare:||Settore BIO/17 - Istologia|
|Data di pubblicazione:||25-mar-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.devcel.2013.01.022|
|Appare nelle tipologie:||01 - Articolo su periodico|