Endoglin is required for myogenic differentiation potential of neural crest stem cells.
Genetic studies show that TGFbeta signaling is essential for vascular development, although the mechanism through which this pathway operates is incompletely understood. Here we demonstrate that the TGFbeta auxiliary coreceptor endoglin (eng, CD105) is expressed in a subset of neural crest stem cells (NCSCs) in vivo and is required for their myogenic differentiation. Overexpression of endoglin in the neural crest caused pericardial hemorrhaging, correlating with altered vascular smooth muscle cell investment in the walls of major vessels and upregulation of smooth muscle alpha-actin protein levels. Clonogenic differentiation assay of NCSCs derived from neural tube explants demonstrated that only NCSC expressing high levels of endoglin (NCSC(CD105+)) had myogenic differentiation potential. Furthermore, myogenic potential was deficient in NCSCs obtained from endoglin null embryos. Expression of endoglin in NCSCs declined with age, coinciding with a reduction in both smooth muscle differentiation potential and TGFbeta1 responsiveness. These findings demonstrate a cell autonomous role for endoglin in smooth muscle cell specification contributing to vascular integrity.
Mancini
Maria L
ML
Center for Molecular Medicine, Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA.
Verdi
Joseph M
JM
Conley
Barbara A
BA
Nicola
Teodora
T
Spicer
Douglas B
DB
Oxburgh
Leif H
LH
Vary
Calvin P H
CP
D000818:Animals; D001483:Base Sequence; D002465:Cell Movement; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000071063:Endoglin; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism
D017931:DNA Primers; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D051785:Smad Proteins