Differential effects of laminin and merosin on neurite outgrowth by developing retinal ganglion cells

In previous work, we showed that cultured avian embryonic retinal ganglion cells (RGC) extend neurites on EHS-laminin early in development, but lose this ability with maturation, as a result of a sharp decline in laminin receptor numbers. Here we show that EHS-laminin promotes neurite outgrowth also from embryonic mammalian RGC, in contrast to previous reports, and that these exhibit similar age-dependent growth responses on laminin. Antibody blocking studies show that this behaviour is mediated in mouse RGC by alpha 6 beta 1 integrin dimers. The laminin isoform merosin is also effective as a neurite outgrowth-promoting substrate for RGC but differs in its ability to elicit a response at advanced stages of development (up to hatching in the chick). Neurite outgrowth by RGC on merosin is inhibited, at all ages, by the function-blocking, anti-beta 1 integrin antibody, CSAT, suggesting that these neurons use alternative alpha beta 1 dimers in their interactions with EHS-laminin and merosin. Together, these findings emphasise the generality of the responsiveness of vertebrate embryonic RGC to laminin during development, and reveal interesting differences in the effects of laminin variants on CNS axon growth and regeneration.