Abstract
The extracellular matrix glycoprotein tenascin-C (TN-C) displays a restricted 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 fibronectin type III (FNIII) domains, which are common to all TN-C isoforms. Unrestricted and independent alternative splicing of six consecutive FNIII cassettes between the fifth and sixth constitutive FNIII domain bears the potential to generate 64 different combinations that might code for TN-C proteins with subtly different functions. To explore TN-C isoform variability in mouse brain, the alternatively spliced region of TN-C mRNAs was examined by the reverse transcription-polymerase chain reaction technique. Polymerase 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 to be expressed in mouse central nervous system, of which 22 are novel. Furthermore, 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 findings highlight the potential role of TN-C in mediating specific neuron glia interactions.
Highlights
The extracellular matrix glycoprotein tenascin-C (TN-C) displays a restricted and developmentally regulated distribution in the mouse central nervous system
A search for additional fibronectin type III (FNIII) domains corresponding either to the A3 domain found in human TN-C or to the newly identified domains AD1 and AD2, which have been shown to be present in both human and chick TN-C (24 –26), was performed using Reverse TranscriptionPolymerase Chain Reaction (RT-PCR) techniques (Fig. 3)
TN-C sequence motifs in different species display a high degree of homology, which reaches 95% for analogous FNIII domains
Summary
The extracellular matrix glycoprotein tenascin-C (TN-C) displays a restricted and developmentally regulated distribution in the mouse central nervous system. We conclude that TN-C is expressed in a complex and regulated pattern in mouse central nervous system These findings highlight the potential role of TN-C in mediating specific neuron glia interactions. TN-C monomers via disulfide bridges to form the native hexameric protein (the hexabrachion; Ref. 2) This region is followed by 14.5 epidermal growth factor-type repeats and eight FNIII domains in the shortest TN-C variant. The diverse functions of the molecule could be localized to distinct functional domains within the protein using proteolytic fragments or fusion proteins encompassing defined structural units of TN-C [17,18,19,20] In this context, the alternatively spliced FNIII domains have attracted particular interest. Fusion proteins consisting of the FNIII domains A1, A2, and A4 (TNfnA124) exhibited repulsive properties, whereas the fusion proteins TNfnBD and, to a lesser extent, TNfnD6 showed a pronounced neurite outgrowth-promoting effect on hippocampal neurons [19]
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