Connexin 43 expression in the mouse embryo: Localization of transcripts within developmentally significant domains

Abstract

The expression of the gap junction gene, Cx43, during mouse embryogenesis was characterized by an in situ hybridization analysis of mouse embryos from gestation days 4.5 to 12.5. This analysis revealed that Cx43 transcripts are differentially expressed as a function of development beginning at the blastocyst stage. In many regions of the embryo, Cx43 transcripts were found in discrete spatially restricted domains. This was observed in conjunction with the development of the brain, neural tube, prevertebra, limb, and various aspects of organogenesis. In some cases, the differential localization of Cx43 transcripts is associated with developmental processes mediated by inductive interactions, such as that of the eye, otic vesicle, kidney, and the branchial arches. In addition, in the 10.5 day embryo, Cx43 transcripts appear to be distributed as a gradient in regions spanning the midbrainhindbrain junction, in the telencephalon, and in the limb mesenchyme. Surprisingly, our results also suggest that neural crest and sclerotomal cells, i.e., cells that are presumably migratory, express high levels of Cx43 transcripts. Overall, these results suggest that gap junctions encoded by Cx43 may play a role in various aspects of mouse development, possibly including relaying second messengers emanating from signal transduction pathways that mediate inductive interactions.

Connexin43 gap junction protein plays an essential role in morphogenesis of the embryonic chick face

“…Spatiotemporal expression patterns of connexin43 protein and Msx-1 transcripts are strikingly similar in developing face (Brown et al, 1993;Minkoff et al, 1997) neural tube (Ruangvoravat and Lo, 1992;Suzuki et al, 1991) and limb (Davidson et al, 1991;Green et al, 1994). Furthermore, retinoic acid treatment of chick embryos not only reduces connexin43 expression, as we have shown here, but also results in decreased Msx-1 expression in facial primordia (Brown et al, 1997).…”

Expression patterns of mRNAs for the gap junction proteins connexin43 and connexin42 suggest their involvement in chick limb morphogenesis and specification of the arterial vasculature

“…Of particular interest, we have found that at early stages of chick limb development (stages 19-20), Cx43 exhibits a graded pattern of expression across the anterior-posterior (AP) axis of the mesoderm of the limb bud, with high amounts of Cx43 being expressed in the posterior mesoderm subjacent to the AER and little Cx43 expression in the anterior mesoderm of the limb bud. Cx43 mRNA also exhibits a graded distribution in the early developing mouse limb bud (Ruangvoravat and Lo, 1992). The graded expression of Cx43 along the AP axis of the mesoderm of the early chick limb bud correlates with a functional gradient of gap junctional communication along the AP axis (Coelho and Kosher, 1991b).…”

“…During early stages of limb development, Cx43 transcripts substantially above background are not detectable in nonridge limb ectoderm, and Cx43 mRNA is expressed in high amounts in the ectopic AER that forms along the anterior periphery of diplopodia-5 mutant limb buds, which directs the outgrowth and formation of supernumerary skeletal elements from the anterior mesoderm of the mutant limb buds. Cx43 is also expressed in the AER of the developing mouse limb bud (Ruangvoravat and Lo, 1992;Laird et al, 1992;Yancey et al, 1992), and extensive gap junctional communication occurs among the cells of both the mouse (Laird et al, 1992) and avian (Wilcox and Kelley, 1993) AER. The absence of abundant Cx43 transcripts in nonridge limb ectoderm interfaces well with the recent observation that, although the cells of the avian AER are coupled to one another, they are apparently not coupled to the dorsal or ventral limb ectoderm (Wilcox and Kelley, 1993).…”

“…Thus, gap junctions comprising different connexins might be involved in mediating different developmental processes. Two members of the connexin family, connexin43 and connexin32, have recently been shown to exhibit nonuniform expression patterns in the developing mouse limb bud (Ruangvoravat and Lo, 1992;Laird et al, 1992;Yancey et al, 1992). However, the expression of various connexins in the developing chick limb bud, which is readily amenable to experimental manipulation and analyses of gap junction function, has not been reported.…”

Differential Expression of Connexins during Neocortical Development and Neuronal Circuit Formation

“…Also, gap junctions may be linked with the migration of neural crest and sclerotomal cells (Ruangvoravat and Lo, 1992). In neocortical development, according to the radial unit hypothesis of Rakic (1988), the ventricular zone consists of proliferative units that provide a protomap of prospective cytoarchitectonic areas.…”