Differential expression of gap junction mRNAs and proteins in the developing murine kidney and in experimentally induced nephric mesenchymes.

Abstract

The expression of three gap junction (GJ) proteins, alpha 1 (Cx43), beta 1 (Cx32), and beta 2 (Cx26), and their transcripts were examined during the ontogeny of the mouse and rat kidney. These proteins were expressed in two non-overlapping patterns. The alpha 1 GJ protein was first observed in mesenchymal cells in the 12-day mouse kidney. By day 14 and thereafter, the alpha 1 protein was detected in the transient S-shaped bodies, but not in the podocytes of the maturing glomeruli. After birth the antigen was retained in a small subset of secretory tubules. The beta 1 and beta 2 GJ proteins were similar in their developmental patterns. They were first detected in a small subset of secretory tubules in the subcortical zone of day 17 embryos. These tubules were identified by immunohistochemical markers to be proximal. At birth, practically all proximal tubules expressed the two antigens. This analysis of GJ proteins was consistent with the results of S1 nuclease protection assays showing that, while the alpha 1 mRNA appeared early during kidney development and declined around birth, the two beta mRNAs appeared later and became intensified during the last days of intrauterine development. In experimentally induced metanephric mesenchymes, a transient expression of the alpha 1 GJ protein was seen during the segregation of the tubular anlagen. beta 1 and beta 2 GJ proteins were not detected in such induced mesenchymes cultivated up to 7 days. These observations provide evidence for the cell-specific utilization of different GJ genes during different stages of kidney organogenesis. The alpha 1 gene is activated during the early segregation of the secretory tubule and might contribute to its compartmentalization, while the beta 1 and beta 2 gene products are not detected until advanced stages of development. The latter gene products might be correlated with the physiological activity of the proximal tubules in vivo, as they are not expressed in experimentally induced tubules detectable with markers for proximal tubules.