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 appro priate 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 alpha3, alpha6, alpha7, and beta1 mRNAs have all been detected in adult rat motoneurons. We have here, by us e of in situ hybridization histochemistry, examined the normal postnatal de velopment 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 re gulation 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 d ays after SNT in the neonatal animal. During postnatal development, there w as a distinct shift in the integrin composition from a stronger expression of the alpha6 subunit to a very clear dominance of alpha7 in the adult. All types of axotomy in the adult rat induced initial (1-7 days) large up-regu lations of alpha 16, alpha7 and beta1 subunit mRNAs (250-500%). Only minor changes for alpha3 mRNA were seen, and beta4 mRNA could not be detected at all in motoneurons. After adult SNT, the alpha7 and pi subunits were up-reg ulated throughout the studied period, and the alpha6 subunit mRNA was event ually normalized. After VRA, however, the alpha7 and beta1 levels peaked ea rlier than after SNT and were normalized at 42 days, whereas alpha6 mRNA wa s up-regulated longer than after SNT. Neonatal SNT had much smaller effects on the expression of the studied subunits. The results suggest that an imp ortant part of the response to axotomy of motoneurons is to up-regulate rec eptors for laminin. The developmental shift in integrin subunit composition and the various responses seen in the lesion models indicate that differen t isofonns of laminin play a role in the regenerative response. (C) 2000 Wi ley-Liss, Inc.