Tenascin knockout mice: barrels, boundary molecules, and glial scars

Abstract

In light of a previous report suggesting that the brains of tenascin- deficient animals are grossly normal, we have studied the somatosensory cortical barrel field and injured cerebral cortex in postnatal homozygous tenascin knockout, heterozygote, and normal wild-type mice. Nissl staining, cytochrome oxidase, and Dil axonal tracing of thalamocortical axonal projections to the somatosensory cortex, all reveal the formation of normal barrels in the first postnatal week in homozygous knockout mice that cannot be distinguished from heterozygote or normal wild-type barrels. In addition to confirming the absence of tenascin in knockout animals, and reporting apparently reduced levels of the glycoprotein in barrel boundaries of heterozygote animals using well-characterized antibodies and immunocytochemistry, we also studied the DSD-1-PG proteoglycan, another developmentally regulated molecule known to be associated with transient glial/glycoconjugate boundaries that surround developing barrels; DSD-1-PG was also found to be expressed in barrel boundaries in apparently normal time frames in tenascin knockout mice. Peanut agglutinin (PNA) binding of galactosyl- containing glycoconjugates also revealed barrel boundaries in all three genotypes. We also examined the expression of tenascin-R, a paralog of tenascin-C (referred to here simply as tenascin). As previously reported, tenascin-R is prominently expressed in subcortical white matter, and we found it was not expressed in the barrel boundaries in any of the genotypes. Thus, the absence of tenascin does not result in a compensatory expression of tenascin-R in the barrel boundaries. Finally, we studied wounds of the cerebral cortex in the late postnatal mouse. The astroglial scar formed, for the most part, in the same time course and spatial distribution in the wild-type and tenascin knockout mice. However, there may be some differences in the extent of gliosis between the knockout and the wild type that warrant further study. Roles for boundary molecules like tenascin during brain pattern formation and injury are reconsidered in light of these findings on barrel development and cortical lesions in tenascin-deficient mice.

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

“…One difference was the increased activation of astrocytes after the AraC treatment. This is consistent with previous reports of increased recruitment of astroglia around CNS wounds in TnC null mice (Steindler et al, 1995) and it will be interesting to investigate the contribution of astrocyte activation to SEZ homeostasis. Astrocytes have been shown to support neurogenesis (Lim and Alvarez-Buylla, 1999), but in cases of injury, reactive astroglia have been shown both to impede (Bahr et al, 1995) and to facilitate (Iseda et al, 2003) tissue regeneration.…”

“…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

“…Single knockouts of neurocan and Tn-C showed no apparent anatomical abnormalities in the CNS (Steindler et al 1995;Zhou et al 2001). A potential compensation by up-regulation of the closely related brevican or Tn-R, respectively, has not been observed.…”

Temporally restricted substrate interactions direct fate and specification of neural precursors derived from embryonic stem cells

“…The function of the ECM might extend beyond morphogenetic effects, because loss or disarrangement of boundaries is observed in CNS diseases and malformations (1,(4)(5)(6) and because the ECM is involved in regulating synaptic plasticity in the adult (7). However, early embryonic lethality in some animal knockout models (8,9) and only minor phenotypic abnormalities in others (10) puzzles the study of individual matrix molecules and their receptors during critical periods of neural development in vivo. ES cells used as a model system for neurogenesis offer an alternative approach in vitro.…”