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 i.v./i.v. 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.

WNT/Frizzled-2 Signaling Induces Aggregation and Adhesion among Cardiac Myocytes by Increased Cadherin–β-Catenin Complex

“…Although the specific role of Wnt-mediated cell adhesion in the formation of various organ compartments is not known, an effect of Wnt on the regulation of intercellular gap junctions has been demonstrated in Xenopus embryos, in vivo (Olson et al, 1991). Cadherin-mediated cell adhesion appears to be a prerequisite for gap junction formation in several cell types (Jongen et al, 1991;Gumbiner et al, 1988), and the abundance of gap junctions can be regulated by both cadherin (Mege et al, 1988) and Wnt (Meyer et al, 1997;van der Heyden et al, 1998). In our study, electrophysiological experiments carried out in our Figure 12.…”

Overexpression of connexin43 alters the mutant phenotype of midgestational wnt‐1 null mice resulting in recovery of the midbrain and cerebellum

“…In addition, wnt ‐ 1 specifically induces expression of Cx43 and increases GJIC in neural crest‐derived PC12 cells and cardiac myocytes (van der Heyden et al,1998; Ai et al,2000). Ectopic expression of wnt ‐ 1 in the mouse limb bud also induces changes in Cx43 expression (Meyer et al,1997). Based on these studies, clearly a regulatory connection exists between wnt ‐ 1 and gap junctions.…”

The Circle of Health

“…Gap junctions are channels between cells made of protein complexes that facilitate communication and increase electrical conductivity (Ewart et al, 1997). Structures with a high density of gap junctions are known as organizing centers (Meyer et al, 1997). These centers perform the role of intercellular communication and growth regulation in the early embryo, preceding the development of other physiological systems such as the nervous system.…”