Regulation of laminin-associated integrin subunit mRNAs in rat spinal motoneurons during postnatal development and after axonal injury.

Two important prerequisites for successful axon regeneration are that appropriate extracellular molecules are available for outgrowing axons and that receptors for such molecules are found in the regenerating neuron. Laminins and their receptors in the integrin family are examples of such molecules, and laminin-associated integrin subunits alpha 3, alpha 6, alpha 7, and beta 1 mRNAs have all been detected in adult rat motoneurons. We have here, by use of in situ hybridization histochemistry, examined the normal postnatal development of the expression in motoneurons of these mRNAs and integrin beta 4 mRNA, all of which have been associated with laminin-2. We studied the regulation of these mRNAs, 1-42 days after two types of axotomy in the adult rat (sciatic nerve transection, SNT; ventral root avulsion, VRA) and 1-10 days after SNT in the neonatal animal. During postnatal development, there was a distinct shift in the integrin composition from a stronger expression of the alpha 6 subunit to a very clear dominance of alpha 7 in the adult. All types of axotomy in the adult rat induced initial (1-7 days) large up-regulations of alpha 6, alpha 7 and beta1 subunit mRNAs (250-500%). Only minor changes for alpha 3 mRNA were seen, and beta 4 mRNA could not be detected at all in motoneurons. After adult SNT, the alpha 7 and beta 1 subunits were up-regulated throughout the studied period, and the alpha 6 subunit mRNA was eventually normalized. After VRA, however, the alpha 7 and beta1 levels peaked earlier than after SNT and were normalized at 42 days, whereas alpha 6 mRNA was up-regulated longer than after SNT. Neonatal SNT had much smaller effects on the expression of the studied subunits. The results suggest that an important part of the response to axotomy of motoneurons is to up-regulate receptors for laminin. The developmental shift in integrin subunit composition and the various responses seen in the lesion models indicate that different isoforms of laminin play a role in the regenerative response. Copyright 2000 Wiley-Liss, Inc.