Ρυθμιστικές αλληλουχίες της 5ης μη μεταγραφόμενης περιοχής του υποκινητή του ανθρώπινου ΤΑΧ-1 γονιδίου καθοδηγούν ειδική έκφραση στο αναπτυσσόμενο κεντρικό νευρικό σύστημα του ποντικού
Upstream regulatory sequenses of the human TAX-1 gene drive specific expression to the developing mouse central nervous system
Διατμηματικό, συνεργαζόμενα Τμήματα Βιολογίας και Ιατρικής. The glycoprotein TAG-1 (named TAX-1 in the human) is a cell adhesion molecule (CAM) belonging to the Ig/FNIII family. TAG-1 is expressed at the earliest stages of axon outgrowth in vivo and has been shown to promote adhesion and neurite outgrowth in vitro via homophilic and heterophilic mechanisms respectively. In the developing human as well as in mouse, TAX-1/TAG-1 expression can be used as a good indicator of axonogenesis. In vivo studies have implicated the molecule in the guidance of commissural axons to the floor plate in embryonic spinal cord. TAG-1 has also been implicated in the differentiation of granule cell precursors in the postnatal cerebellum. In addition, TAG-1 is expressed in many different neuronal populations in the central nervous system (CNS) during development and postnatal growth. As an initial step to understand the molecular mechanisms that underlie this complex pattern of expression, we have begun the functional dissection of regulatory sequences of the TAX-1 gene using transgenic mouse analysis. We isolated genomic fragments of the TAX-1 locus and used them to drive the expression of the reporter gene LacZ in transgenic mice. A total of seven independent lines have been obtained with a construct containing 4 Kb of TAX-1 upstream sequence. Preliminary results show that the construct is able to partially recapitulate the endogenous pattern of TAG-1 expression in the developing CNS. In particular, expression is detected as early as embryionic day 11 and persists through adulthood. It is detected in the cerebellar primordium, hippocampus and several nuclei in the embryonic and postnatal mouse CNS.