Tenascin-C Is an Inhibitory Boundary Molecule in the Developing Olfactory Bulb

Abstract

We recently described the boundary-like expression pattern of the extracellular matrix (ECM) molecule Tenascin-C (Tnc) in the developing mouse olfactory bulb (OB) (Shay et al., 2007). In the present study we test the hypothesis that Tnc inhibits olfactory sensory neuron (OSN) axon growth in the developing olfactory bulb (OB) prior to glomerulogenesis. The period of time before glomerular formation begins, when axons remain restricted to the developing olfactory nerve layer (ONL), is crucial for axon sorting. Here, we show with in vitro analyses that OSN neurite outgrowth is inhibited by Tnc in a dose dependent manner, and that in stripe assays, axons preferentially avoid Tnc. Using Tnc null mice, we also show that that glomerular development is delayed in the absence of Tnc. In wild type mice, OSN axons coalesce into immature or protoglomeruli, which further differentiate and segregate into glomeruli. Glomeruli are first identifiable as discrete structures at birth. In null mice, glomeruli appear immature at birth, remain fused to the ONL and have a significantly larger diameter compared to wild type controls. By postnatal day 4, null glomeruli are indistinguishable from controls. Thus, OSN axons appear delayed in their coalescence into glomerular structures. These data correlate with behavioral reports of Tnc null mice which are delayed by 24 hours in their acquisition of an olfactory behavior (de Chevigny et al., 2006). Collectively, these data demonstrate that Tnc is an inhibitory boundary molecule in the developing OB during a key period of development.

HNK-1 Epitope-carrying Tenascin-C Spliced Variant Regulates the Proliferation of Mouse Embryonic Neural Stem Cells

“…By proteomic analysis using LC-MS/MS, we identified TNC as a major carrier protein of HNK-1 in NSCs. TNC is well known as an ECM protein that is expressed prominently during brain development in the olfactory bulb, ventricular zone, and subventricular zone (38,40,41). In mouse brain tissues, TNC possesses six alternatively spliced domains (Fig.…”

Tenascin-C: Form versus function

“…Tenascin-C is abundantly expressed in the mouse olfactory bulb, ventricular zone (VZ) and sub ventricular zone (SVZ) of the CNS during development and postnatally [65][66][67] where it has been shown to orchestrate the development of niches permitting the development of neural stem cells (NSC) altering their response to FGF-2 and BMP-4. 68 Embryonic and postnatal day 6 mouse cerebellum express 4 and 27 different major mRNA isoforms respectively, of which the largest decrease in expression faster than the shorter variants during neural development.…”

Extracellular Matrix: Functions in the Nervous System

“…In NSCs in culture, TN-C facilitates the switch from production of neuronal to glial progenitors (Lillien and Raphael 2000;Garcion et al 2004;Liao et al 2008), whereas TN-R inhibits migration of NSC-derived neurons (Huang et al 2009). In vivo, TN-C regulates myelinating glial lineage development and glomerulogenesis in the olfactory bulbs (OBs) (Garcion et al 2001;Treloar et al 2009). TN-R promotes detachment of chain-migrating neuroblasts in the RMS and their migration within the OBs.…”

“…Although no axonal pathfinding defects have been reported in TN-R mutant mice, TN-R acts as a repellent for optic axons in zebrafish (Becker et al 2003;Becker et al 2004). In the OB, TN-C is an inhibitory boundary molecule, preventing axonal growth of sensory neurons before glomerulogenesis (Treloar et al 2009). …”