Evidence for combinatorial variability of tenascin-C isoforms and developmental regulation in the mouse central nervous system

The extracellular matrix glycoprotein tenascin-C (TN-C) displays a restrict ed and developmentally regulated distribution in the mouse central nervous system. Defined modules of the molecule have been shown to mediate specific functions, such as neuron migration, neurite outgrowth, cell adhesion, and cell proliferation. The smallest TN-C form contains a stretch of eight fib ronectin type III (FNIII) domains, which are common to all TN-C isoforms, U nrestricted and independent alternative splicing of six consecutive FNIII c assettes between the fifth and sixth constitutive FNIII domain bears the po tential to generate 64 different combinations that might code for TN-C prot eins with subtly different functions. To explore TN-C isoform variability i n mouse brain, the alternatively spliced region of TN-C mRNAs was examined by the reverse transcription-polymerase chain reaction technique. Polymeras e chain reaction products of uniform size were subcloned and analyzed using domain-specific probes to reveal the expression of particular combinations of alternatively spliced FNIII domains. 27 TN-C isoforms were identified t o be expressed in mouse central nervous system, of which 22 are novel. Furt hermore, during development, specific TN-C isoforms were found to occur in distinct relative frequencies, as demonstrated for isoforms containing two alternatively spliced FNIII domains. We conclude that TN-C is expressed in a complex and regulated pattern in mouse central nervous system. These find ings highlight the potential role of TN-C in mediating specific neuron glia interactions.