Developmental regulation and asymmetric expression of the gene encoding Cx43 gap junctions in the mouse limb bud

Abstract

The Gja1 gene encoding the gap junction connexin 43 (Cx43) is dynamically regulated during limb morphogenesis. Transcript expression is found in many regions of the limb bud known to be important in regulating limb growth and patterning. In the newly emerged limb bud, Gja1 transcripts 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 the ventrodistal ectoderm is initiated left/right asymmetrically, with some strain backgrounds showing reverse sidedness in the fore vs. hindlimb buds. In legless, a mouse mutant exhibiting both limb and left/right patterning defects, Gja1 transcripts could not be detected in this region. However, in the iv/iv embryo, a mutant with randomization of body situs, the same pattern of Gja1 asymmetry was found in the limb ectoderm regardless of body situs. This suggests that Gja1 transcript expression is not directly linked to signaling pathways involved in specification of the left/right axis. In addition to transcript expression in the apical ectodermal ridge, Gja1 transcripts were also found at high levels in the ventral ectoderm. In the limb bud mesenchyme, Gja1 transcripts were distributed in a posterior‐distal gradient, coincident with tissue known to have polarizing activity. With limb outgrowth and the initiation of limb mesenchyme condensation, Gja1 transcripts were localized in the presumptive progress zone, and in the condensing mesenchyme. In more proximal regions of the limb where mesenchyme differentiation has been initiated, Gja1 transcripts were expressed only in the outer mesenchymal cells comprising the presumptive perichondrium. Further analysis of transgenic mice ectopically expressing Wnt‐1 in the limb mesenchyme revealed alterations in the pattern of Gja1 transcript expression in conjunction with the perturbation of limb mesenchyme condensation and differentiation. Together, these findings indicate that Cx43 gap junctions may mediate cell‐cell interactions important in cell signaling processes involved in limb growth and patterning. Dev. Genet. 21:290–300, 1997. © 1997 Wiley‐Liss, Inc.

The Apical Ectodermal Ridge: morphological aspects and signaling pathways

“…By E10.5-11, corresponding to stage 3 of Wanek et al (1989), a linear and compact AER with a polystratified epithelial structure (3-4 layers) has formed and positioned itself at the distal DV border of the bud ( Fig. 2B; Kelley and Fallon, 1983;Meyer et al, 1997;Bell et al, 1998). The notch observed at the base of the avian AER is never observed in the mammalian ridge (Kelley, 1973).…”

Lithium Chloride Regulates Connexin43 in Skeletal Myoblasts In Vitro: Possible Involvement in Wnt/β-Catenin Signaling

“…Wnt-1 gene has been shown to promote gap-junctional communication between ventral cells of the developing Xenopus embryo (Olson et al 1991(Olson et al , 1992. In addition, the ectopic expression of Wnt-1 in the limb mesenchyme of transgenic mice increases the local accumulation of Cx43 transcripts (Meyer et al 1997). In rat pheochromocytoma (PC12) cells, a study suggests that Cx43 gene may be a downstream target of Wnt-1 signaling (van der Heyden et al 1998).…”

Wnt-1 regulation of connexin43 in cardiac myocytes

“…Wnt-1 has been shown to enhance gap junctional communication between ventral cells of the developing Xenopus embryo (17,18). In addition, ectopic expression of Wnt-1 in the limb mesenchyme of transgenic mice increases the local accumulation of Cx43 transcripts (19). The mechanisms leading to these effects are uncertain, but recent studies in rat pheochromocytoma (PC12) cells suggest that the Cx43 gene may be a downstream target of Wnt-1 signaling (20).…”