The cell recognition molecule CHL1 is strongly upregulated by injured and regenerating thalamic neurons

Abstract

Close homologue of L1 (CHL1) is a cell recognition molecule known to promote axonal growth in vitro. We have investigated the expression of CHL1 mRNA by regenerating central nervous system (CNS) neurons, by using in situ hybridisation 3 days to 10 weeks following the implantation of living and freeze-killed peripheral nerve autografts into the thalamus of adult rats. At all survival times after implantation of living grafts, neurons of the thalamic reticular nucleus (TRN), close to the graft tip and up to 1 mm away from it, displayed strong signal for CHL1 mRNA, even though TRN neurons show very low levels of CHL1 mRNA expression in unoperated animals. When the cell bodies of regenerating neurons were identified by retrograde labelling from the distal portion of the grafts, 4-6 weeks after operation, most of the labelled cells were found in the TRN and could be shown to haveupregulated CHL1 mRNA. In addition, some neurons in dorsal thalamic nuclei near the graft tip transiently upregulated CHL1 mRNA during the first 3 weeks after graft implantation, and glial cells showing CHL1 mRNA expression were present at the brain/graft interface 3 days to 2 weeks after operation. Freeze-killed grafts, into which axons do not regenerate, caused a transient upregulation of CHL1 in very few TRN neurons near the graft tip and in glial cells at the brain/graft interface but did not produce prolonged CHL1 mRNA expression. CHL1 can therefore be added to the list of molecules (including GAP-43, L1, and c-jun) strongly expressed by CNS neurons that regenerate their axons into nerve grafts, but not by those neurons that fail to regenerate their axons.

Delayed Applications of L1 and Chondroitinase ABC Promote Recovery after Spinal Cord Injury

“…Retinal ganglion cells, nigrostriatal and cholinergic neostriatal neurons express relatively high levels of L1, and are able to regenerate axons along a peripheral nerve graft without upregulation of L1 expression (Becker et al, 2001;Jung et al, 1997;Woolhead et al, 1998). Neurons in the thalamic reticular nucleus express low levels of L1 and CHL1, but are capable of upregulating these proteins, and also successfully regrow into the graft (Chaisuksunt et al, 2000a;Zhang et al, 1995). Cerebellar deep nucleus neurons and precerebellar brainstem neurons also show a substantial capacity for axon regeneration, accompanied by increased expression of L1 (Chaisuksunt et al, 2000b).…”

Close Homolog of L1 Is an Enhancer of Integrin-mediated Cell Migration

“…Schwann cell migration on regenerating nerves is supported by collagens I, III, IV, and fibronectin, which, along with ␣ 1 ␤ 1 integrin, increase at the injury site (41,77,78). CHL1 expression is also up-regulated in dorsal root ganglion and thalamic neurons upon injury (23,79) and is a strong promoter of neurite growth (20), suggesting that it may function analogously to promote axon growth on extracellular matrix substrates. The ability of CHL1 to promote cell migration toward extracellular matrix proteins may also play a role in radial glia-guided migration of cortical neurons in the developing neocortex, where integrin receptors and their ligands are distributed (80) and CHL1 is prominently expressed (21).…”

Glial Scar Expression of CHL1, the Close Homolog of the Adhesion Molecule L1, Limits Recovery after Spinal Cord Injury

“…After injuries of the adult mouse CNS and peripheral nervous system, CHL1 is upregulated in its expression in both neurons and astrocytes (Chaisuksunt et al, 2000;Zhang et al, 2000;Rolf et al, 2003). The functional consequences of this posttraumatic response have, however, remained unknown.…”