Expression and function of integrin alpha4beta1 and vascular cell adhesion molecule-1 (VCAM-1) during sympathetic innervation of the heart.
The interaction between the integrin alpha4beta1 receptor on superior cervical ganglion (SCG) neurons and vascular cell adhesion molecule-1 (VCAM-1) in cardiac tissue has been implicated in proper development of the sympathetic innervation of the heart (Wingerd et al. [2002] J Neurosci 22:10772-10780). In this study, we examined the expression and function of alpha4beta1 and VCAM-1 in developing rat SCG and heart. In vitro, the alpha4beta1-dependent neurite outgrowth on VCAM-1 decreased by approximately 50% from postnatal day 1 to 6. This down-regulation was correlated with a shift in alpha4 isoform and a shift in alpha4 localization from neurites to cell bodies. This altered localization was also observed in vivo but on a different time scale. alpha4 was detected on most developing SCG neurons and on macrophages and blood vessels. In the heart, alpha4 was detected on sympathetic axons, but the percentage of alpha4-positive fibers decreased with age. VCAM-1 immunoreactivity was abundant in heart tissue throughout development, in close proximity to sympathetic axons. The regulation of alpha4beta1 function, and localization of alpha4 and VCAM-1, are consistent with a role for the alpha4beta1--VCAM-1 interaction in extension of sympathetic axons into the myocardium.
Wingerd
Kevin L
KL
Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
Goodman
Nichol L
NL
Leu
Sergiu T
ST
Clegg
Dennis O
DO
D000818:Animals; D002478:Cells, Cultured; D006321:Heart / Q000196:embryology* / Q000294:innervation*; D007150:Immunohistochemistry; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1