Knock-in of integrin beta 1D affects primary but not secondary myogenesis in mice.
Integrins are extracellular matrix receptors composed of alpha and beta subunits involved in cell adhesion, migration and signal transduction. The beta1 subunit has two isoforms, beta 1A ubiquitously expressed and beta 1D restricted to striated muscle. They are not functionally equivalent. Replacement of beta 1A by beta 1D (beta 1D knock-in) in the mouse leads to midgestation lethality on a 50% Ola/50% FVB background [Baudoin, C., Goumans, M. J., Mummery, C. and Sonnenberg, A. (1998). Genes Dev. 12, 1202-1216]. We crossed the beta 1D knock-in line into a less penetrant genetic background. This led to an attenuation of the midgestation lethality and revealed a second period of lethality around birth. Midgestation death was apparently not caused by failure in cell migration, but rather by abnormal placentation. The beta 1D knock-in embryos that survived midgestation developed until birth, but exhibited severely reduced skeletal muscle mass. Quantification of myotube numbers showed that substitution of beta 1A with beta 1D impairs primary myogenesis with no direct effect on secondary myogenesis. Furthermore, long-term primary myotube survival was affected in beta 1D knock-in embryos. Finally, overexpression of beta 1D in C2C12 cells impaired myotube formation while overexpression of beta 1A primarily affected myotube maturation. Together these results demonstrate for the first time distinct roles for beta1 integrins in primary versus secondary myogenesis and that the beta 1A and beta 1D variants are not functionally equivalent in this process.
Cachaço
Ana Sofia
AS
Department of Animal Biology and Centre for Environmental Biology, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal.
Chuva de Sousa Lopes
Susana M
SM
Kuikman
Ingrid
I
Bajanca
Fernanda
F
Abe
Kuniya
K
Baudoin
Christian
C
Sonnenberg
Arnoud
A
Mummery
Christine L
CL
Thorsteinsdóttir
Sólveig
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D017403:In Situ Hybridization; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development / Q000502:physiology*
D019012:Integrin beta1