Nerve growth factors and molecules of the extracellular matrix in neuronal development.

The survival of developing neurons is epigenetically regulated by trophic factors. Only one such protein, the nerve growth factor (NGF) has been shown to act in vivo, where it supports the survival of neural-crest-derived sensory and sympathetic neurons. Recently, however, other proteins have been isolated and shown to support the survival of cultured neurons. Furthermore, in addition to the effects of soluble trophic factors, proteins of the extracellular matrix are also able to modulate neuronal survival. Analysis of the basal lamina protein, laminin, shows that when used as a culture substrate it stimulates neurite outgrowth and potentiates neuronal survival via a site associated with its heparin binding domain. On proteolytic cleavage of laminin, however, a cryptic site is unmasked that can also promote neuronal survival and neurite growth. The properties of this cryptic site indicate that it may be similar to that of the laminin-like molecule synthesized by Schwann cells, which although recognized by anti-laminin antibodies is not inhibited by them.