Enhanced expression of the developmentally regulated extracellular matrix molecule tenascin following adult brain injury.

Abstract

Tenascin is an extracellular matrix molecule synthesized and released by young astrocytes during embryonic and early postnatal development of the nervous system, and it is concentrated in boundaries around emerging functional neuronal units. In the adult nervous system, tenascin can be detected only in very low levels. Distinct spatial and temporal distributions of tenascin during developmental events suggest a role in the guidance and/or segregation of neurons and their processes within incipient functional patterns. We show here, using in situ hybridization and immunocytochemistry, that stab wounds of the adult mouse cerebellar and cerebral cortices result in an enhanced expression of tenascin in a discrete region around the lesion site that is associated with a subset of glial fibrillary acidic protein-positive astrocytes. Tenascin upregulation in the lesioned adult brain may be directly involved in failed regeneration or indirectly involved through its interactions with other glycoconjugates that either inhibit or facilitate neurite growth.Extracellular matrix (ECM) molecules may have important roles during embryonic development, possibly acting as permissive substrates that help guide cells and their processes to their targets (1). Other types of ECM molecules that have only recently been described in the central nervous system (CNS) [e.g., sulfated proteoglycans (2)] could have inhibitory functions and form barriers to growth.The tenascin molecule is an oligomeric glycoprotein constituent of the ECM that carries the carbohydrate epitope characteristic ofthe L2/HNK-1 family ofadhesion molecules (3, 4). It is referred to variously (3) as hexabrachion, glioma mesenchymal extracellular matrix protein, J1, or cytotactin. In the developing CNS, tenascin is synthesized and expressed by young astrocytes possibly mediating certain neuron-glia interactions (5). Even though the molecule is widely distributed in many different tissues during development and hyperplasia (e.g., in cartilage, regions of epithelialmesenchymal interactions, tumors) (3), in the CNS it exhibits site-restricted expression (6,7). This latter attribute of tenascin distribution prompted the designation of these regions as "boundaries," where dense accumulations of this and other glycoconjugates (i.e., glycoproteins, glycolipids, or glycosaminoglycans) cordon off emerging neuronal arrays (8). The possible biological actions of tenascin have been assayed in culture paradigms using neural (e.g., neural crest, neurons, and astrocytes) and nonneural (e.g., fibroblasts) cells, with evidence for inhibition and promotion of migration and process outgrowth (9)(10)(11)(12).The presence or absence of tenascin in or around lesion sites may have important implications for the sequelae of CNS injury. Here, we examine the effects of cerebellar and cerebral cortical lesions on tenascin expression in the adult mouse. The current study presents in situ hybridization and immunocytochemical data showing an enhanced expression of astrocytic tenascin associat...

The Adult Mouse Subependymal Zone Regenerates Efficiently in the Absence of Tenascin-C

“…1). Although expression of TnC bordering areas of dynamic cell movements and interactions has been well documented during development (Steindler et al, 1995) and after injury (Laywell et al, 1992;Gates et al, 1996;Nishio et al, 2005), its role remains elusive (Nishio et al, 2005). The only difference we detected within the SEZ of the TnC deficient mice was the increased number of type-A cell clusters along the LV wall.…”

“…Tenascin-C (TnC) is a large ECM glycoprotein (Jones and Jones, 2000) that is expressed in the brain neurogenic zones during development (Steindler et al, 1995;Garcion et al, 2004) and postnatally (Thomas et al, 1996;Garcion et al, 2001;Peretto et al, 2005;Bonnert et al, 2006;de Chevigny et al, 2006) as well as in areas of plasticity (i.e., after injury) in the adult brain (Laywell et al, 1992;Gates et al, 1996;Nishio et al, 2005). This expression profile combined with results using TnC null mice showing a role for TnC in the proliferation and migration of early postnatal neural precursors (Garcion et al, 2001) and the growth-factor responsiveness of embryonic neural stem cells (NSC) (Garcion et al, 2004) led us to ask whether TnC also plays a role in adult neurogenesis.…”

Extracellular matrix of the central nervous system: from neglect to challenge

“…The lesion and consequent reactive processes induce a matrix accumulation that strongly resembles the juvenile-type of meshwork previously observed during early nervous system development. For instance, surgical incisions in the cerebral cortex or spinal cord provoke a relatively fast and transient up-regulation of Tn-C and neurocan (Asher et al 2000;Haas et al 1999;Jones et al 2003;Laywell et al 1992;Matsui et al 2002;McKeon et al 1999;Tang et al 2003). Also the expression of versican V2, brevican and phosphacan appear to be aVected.…”

Genomic Expression Systems on Hierarchy and Network Leading to Hypertension: Long on History, Short on Facts.

“…At the same time, reactivated astrocytes migrate to the injured area, where they proliferate and produce extracellular matrix (51)(52)(53), thereby reconstituting the blood-brain barrier (Fig. 4).…”