DEVELOPMENTAL REGULATION AND ASYMMETRIC EXPRESSION OF THE GENE ENCODING CX43 GAP-JUNCTIONS IN THE MOUSE LIMB BUD

The Gja1 gene encoding the gap junction connexin 43 (Cx43) is dynamica lly regulated during limb morphogenesis. Transcript expression is foun d in many regions of the limb bud known to be important in regulating limb growth and patterning. In the newly emerged limb bud, Gja1 transc ripts are first expressed in the ventrodistal margin of the ectoderm, and later transcript expression is localized to the apical ectodermal ridge (AER). interestingly transcript expression in;he ventrodistal ec toderm is initiated left/right asymmetrically, with some strain backgr ounds showing reverse sidedness in the Fore vs, hindlimb buds. in legl ess, a mouse mutant exhibiting both limb and left/right patterning def ects, Gja1 transcripts could not be detected in this region. However, in the iv/iv embryo, a mutant with randomization of body situs, the sa me pattern of Gja1 asymmetry was found in the limb ectoderm regardless of body situs. This suggests that Gja1 transcript expression is not d irectly linked to signaling pathways involved in specification of the left/right axis. in addition to transcript expression in the apical ec todermal ridge, Gja1 transcripts were also found at high levels in the Ventral ectoderm. in the limb bud mesenchyme, Gja1 transcripts were d istributed in a posterior-distal gradient, coincident with tissue know n to have polarizing activity. With limb outgrowth and the initiation of limb mesenchyme condensation, Gja1 transcripts were localized in th e presumptive progress zone, and in the condensing mesenchyme. in more proximal regions of the limb where mesenchyme differentiation hers be en initiated, Gja1 transcripts were expressed only in the outer mesenc hymal cells comprising the presumptive perichondrium. Further analysis of transgenic mice ectopically expressing VVnt-1 in the limb mesenchy me revealed alterations in the pattern of Gja1 transcript expression i n conjunction with the perturbation of limb mesenchyme condensation an d differentiation. Together, these findings indicate that Cx43 gap jun ctions may mediate cell-cell interactions important in cell signaling processes involved in limb growth and patterning. (C) 1997 Wiley-Liss, Inc.