DEVELOPMENTAL REGULATION OF CONNEXIN40 GENE-EXPRESSION IN MOUSE HEARTCORRELATES WITH THE DIFFERENTIATION OF THE CONDUCTION SYSTEM

In adult mouse heart, CX40 is expressed in the atria and the proximal part of the ventricular conduction system (the His bundle and the uppe r parts of the bundle branches). This cardiac tissue is specialized in the conduction of the electrical impulse. CX40 is the only mouse conn exin known to be expressed in these parts of the adult conductive tiss ue and is thus considered as a marker of the conduction system. In the present report, we investigated CX40 expression and distribution duri ng mouse heart development. We first demonstrate that CX40 mRNA is reg ulated throughout development, as are other heart connexin transcripts , i.e., CX37, CX43, and CX45, with a decreasing abundance as developme nt proceeds. We also show that the CX40 transcript and protein are sim ilarly regulated, CX40 being expressed as two different phosphorylated and un-phosphorylated forms of 41 and 40 kDa, respectively. Surprisin gly, distribution studies demonstrated that CX40 is widely expressed i n 11 days post-coitum (dpc) embryonic heart, where it is detected in b oth the atria and ventricle primordia. As development proceeds, the CX 40 distribution pattern in the atria is maintained, whereas a more dyn amic pattern is observed in the ventricles. From 14 dpc onwards, as th e adult ventricular conduction system differentiates, CX40 decreases i n the trabecular network and it is preferentially distributed in the v entricular conduction system. CX40 is thus the marker of the early dif ferentiating conduction system. It is hypothesized that the conduction system is present in unorganized ''embryonic'' form at 11 dpc and tra ns-differentiates by 14 dpc into the adult conduction system. (C) 1995 Wiley-Liss, Inc.