Central role of the alpha4beta1 integrin in the coordination of avian truncal neural crest cell adhesion, migration, and survival.

Based on functional and histological studies, the fibronectin receptor of the integrin family alpha4beta1 has been ascribed a critical role during neural crest cell migration in the vertebrate embryo. In the present study, because integrins have been shown to participate in multiple basic cellular processes, including cell adhesion, migration, survival, proliferation, and differentiation, we have reexamined in detail the role of alpha4beta1 during avian truncal neural crest cell migration. RT-PCR and immunocytochemical studies revealed that migrating neural crest cells but not premigratory cells explanted in vitro expressed detectable levels of alpha4 messengers and proteins suggesting that alpha4beta1 expression was induced at the time of the initiation of the migration phase. In agreement with this observation, antibody inhibition of alpha4beta1 activity in vitro resulted in a strong, immediate and sustained reduction of neural crest cell motion on fibronectin, as judged on videomicroscopy analyses, but apparently did not prevent their delamination from the neural tube. However, alpha4beta1 appeared to exhibit a broader role in the control of cell migration on a variety of extracellular matrix molecules, presumably by regulating cellular events downstream from integrins. Moreover, blocking alpha4beta1 function caused a severe increase in apoptotic cell death among the neural crest population without influencing notably cell proliferation. Collectively, these results indicate that, notwithstanding its critical implication in cell motion, alpha4beta1 integrin could play a central role in neural crest cell development by coordinating multiple cellular events, such as cell adhesion, locomotion, and survival. Copyright 2001 Wiley-Liss, Inc.