Developmental expression of sodium entry pathways in rat nephron

During the past several years, sites of expression of ion transport protein s in tubules from adult kidneys have been described and correlated with fun ctional properties. Less information is available concerning sites of expre ssion during tubule morphogenesis, although such expression patterns may be crucial to renal development. In the current studies, patterns of renal ax ial differentiation were defined by mapping the expression of sodium transp ort pathways during nephrogenesis in the rat. Combined in situ hybridizatio n and immunohistochemistry were used to localize the Na-P-i cotransporter t ype 2 (NaPi2), the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), the thiazide-sensitive Na-Cl cotransporter (NCC), the Na/Ca exchanger (NaCa), the epithelial sodium channel (rENaC), and 11 beta-hydroxysteroid dehydroge nase (11HSD). The onset of expression of these proteins began in post-S-sha pe stages. NKCC2 was initially expressed at the macula densa region and lat er extended into the nascent ascending limb of the loop of Henle (TAL), whe reas differentiation of the proximal tubular part of the loop of Henle show ed a comparatively retarded onset when probed for NaPi2. The NCC was initia lly found at the distal end of the nascent distal convoluted tubule (DCT) a nd later extended toward the junction with the TAL. After a period of chang ing proportions, subsegmentation of the DCT into a proximal part expressing NCC alone and a distal part expressing NCC together with NaCa was evident. Strong coexpression of rENaC and 11HSD was observed in early nascent conne cting tubule (CNT) and collecting ducts and later also in the distal portio n of the DCT. Ontogeny of the expression of NCC, NaCa, 11HSD, and rENaC in the late distal convolutions indicates a heterogenous origin of the CNT. Th ese data present a detailed analysis of the relations between the anatomic differentiation of the developing renal tubule and the expression of tubula r transport proteins.