During the past several years, sites of expression of ion transport proteins in tubules from adult kidneys have been described and correlated with functional properties. Less information is available concerning sites of expression during tubule morphogenesis, although such expression patterns may be crucial to renal development. In the current studies, patterns of renal axial differentiation were defined by mapping the expression of sodium transport pathways during nephrogenesis in the rat. Combined in situ hybridization and immunohistochemistry were used to localize the Na-P_i cotransporter type 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-hydroxysteroid dehydrogenase (11HSD). The onset of expression of these proteins began in post-S-shape stages. NKCC2 was initially expressed at the macula densa region and later extended into the nascent ascending limb of the loop of Henle (TAL), whereas differentiation of the proximal tubular part of the loop of Henle showed a comparatively retarded onset when probed for NaPi2. The NCC was initially found at the distal end of the nascent distal convoluted tubule (DCT) and later extended toward the junction with the TAL. After a period of changing 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 connecting tubule (CNT) and collecting ducts and later also in the distal portion 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. These data present a detailed analysis of the relations between the anatomic differentiation of the developing renal tubule and the expression of tubular transport proteins.

nephrogenesis; ion transport; tubular segmentation; mineralocorticoids; rat kidney

This article has been cited by other articles:

				J. Stubbe, K. Madsen, F. T. Nielsen, R. K. Bonde, O. Skott, and B. L. Jensen Postnatal adrenalectomy impairs urinary concentrating ability by increased COX-2 and leads to renal medullary injury Am J Physiol Renal Physiol, September 1, 2007; 293(3): F780 - F789. [Abstract] [Full Text] [PDF]

				M. Baserga, M. A. Hale, Z. M. Wang, X. Yu, C. W. Callaway, R. A. McKnight, and R. H. Lane Uteroplacental insufficiency alters nephrogenesis and downregulates cyclooxygenase-2 expression in a model of IUGR with adult-onset hypertension Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1943 - R1955. [Abstract] [Full Text] [PDF]

				H.-W. Lee, W.-Y. Kim, H.-K. Song, C.-W. Yang, K.-H. Han, H. M. Kwon, and J. Kim Sequential expression of NKCC2, TonEBP, aldose reductase, and urea transporter-A in developing mouse kidney Am J Physiol Renal Physiol, January 1, 2007; 292(1): F269 - F277. [Abstract] [Full Text] [PDF]

				J. L. Pluznick and S. C. Sansom BK channels in the kidney: role in K+ secretion and localization of molecular components Am J Physiol Renal Physiol, September 1, 2006; 291(3): F517 - F529. [Abstract] [Full Text] [PDF]

				M. Baserga, M. A. Hale, X. Ke, Z. M. Wang, X. Yu, C. W. Callaway, R. A. McKnight, and R. H. Lane Uteroplacental insufficiency increases p53 phosphorylation without triggering the p53-MDM2 functional circuit response in the IUGR rat kidney Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R412 - R418. [Abstract] [Full Text] [PDF]

				K. Thomsen and D. G. Shirley A hypothesis linking sodium and lithium reabsorption in the distal nephron Nephrol. Dial. Transplant., April 1, 2006; 21(4): 869 - 880. [Abstract] [Full Text] [PDF]

				F. McCulloch, R. Chambrey, D. Eladari, and J. Peti-Peterdi Localization of connexin 30 in the luminal membrane of cells in the distal nephron Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1304 - F1312. [Abstract] [Full Text] [PDF]

				J. L. Pluznick, P. Wei, P. R. Grimm, and S. C. Sansom BK-{beta}1 subunit: immunolocalization in the mammalian connecting tubule and its role in the kaliuretic response to volume expansion Am J Physiol Renal Physiol, April 1, 2005; 288(4): F846 - F854. [Abstract] [Full Text] [PDF]

				F. Quentin, R. Chambrey, M. M. Trinh-Trang-Tan, M. Fysekidis, M. Cambillau, M. Paillard, P. S. Aronson, and D. Eladari The Cl-/HCO3- exchanger pendrin in the rat kidney is regulated in response to chronic alterations in chloride balance Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1179 - F1188. [Abstract] [Full Text] [PDF]

				A. Nissant, S. Lourdel, S. Baillet, M. Paulais, P. Marvao, J. Teulon, and M. Imbert-Teboul Heterogeneous distribution of chloride channels along the distal convoluted tubule probed by single-cell RT-PCR and patch clamp Am J Physiol Renal Physiol, December 1, 2004; 287(6): F1233 - F1243. [Abstract] [Full Text] [PDF]

				W. Tian, M. Salanova, H. Xu, J. N. Lindsley, T. T. Oyama, S. Anderson, S. Bachmann, and D. M. Cohen Renal expression of osmotically responsive cation channel TRPV4 is restricted to water-impermeant nephron segments Am J Physiol Renal Physiol, July 1, 2004; 287(1): F17 - F24. [Abstract] [Full Text] [PDF]

				S. W. Kim, W. Wang, J. Nielsen, J. Praetorius, T.-H. Kwon, M. A. Knepper, J. Frokiaer, and S. Nielsen Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats Am J Physiol Renal Physiol, May 1, 2004; 286(5): F922 - F935. [Abstract] [Full Text] [PDF]

				K. Madsen, J. Stubbe, T. Yang, O. Skott, S. Bachmann, and B. L. Jensen Low endogenous glucocorticoid allows induction of kidney cortical cyclooxygenase-2 during postnatal rat development Am J Physiol Renal Physiol, January 1, 2004; 286(1): F26 - F37. [Abstract] [Full Text] [PDF]

				V. Campean, F. Theilig, A. Paliege, M. Breyer, and S. Bachmann Key enzymes for renal prostaglandin synthesis: site-specific expression in rodent kidney (rat, mouse) Am J Physiol Renal Physiol, July 1, 2003; 285(1): F19 - F32. [Abstract] [Full Text] [PDF]

				J. Stubbe, B. L. Jensen, S. Bachmann, P. Morsing, and O. Skott Cyclooxygenase-2 contributes to elevated renin in the early postnatal period in rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2003; 284(5): R1179 - R1189. [Abstract] [Full Text] [PDF]

				R. Schmitt, E. Klussmann, T. Kahl, D. H. Ellison, and S. Bachmann Renal expression of sodium transporters and aquaporin-2 in hypothyroid rats Am J Physiol Renal Physiol, May 1, 2003; 284(5): F1097 - F1104. [Abstract] [Full Text] [PDF]

				J. Loffing and B. Kaissling Sodium and calcium transport pathways along the mammalian distal nephron: from rabbit to human Am J Physiol Renal Physiol, April 1, 2003; 284(4): F628 - F643. [Abstract] [Full Text] [PDF]

				J. B. Wade Distribution of transporters along the mouse distal nephron: something old, something borrowed, something new Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1019 - F1020. [Full Text] [PDF]

				C. Nicco, M. Wittner, A. DiStefano, S. Jounier, L. Bankir, and N. Bouby Chronic Exposure to Vasopressin Upregulates ENaC and Sodium Transport in the Rat Renal Collecting Duct and Lung Hypertension, November 1, 2001; 38(5): 1143 - 1149. [Abstract] [Full Text] [PDF]

				P. Gallardo, L. P. Cid, C. P. Vio, and F. V. Sepulveda Aquaporin-2, a regulated water channel, is expressed in apical membranes of rat distal colon epithelium Am J Physiol Gastrointest Liver Physiol, September 1, 2001; 281(3): G856 - G863. [Abstract] [Full Text] [PDF]

				H. Hager, T.-H. Kwon, A. K. Vinnikova, S. Masilamani, H. L. Brooks, J. Frokiaer, M. A. Knepper, and S. Nielsen Immunocytochemical and immunoelectron microscopic localization of {alpha}-, {beta}-, and {gamma}-ENaC in rat kidney Am J Physiol Renal Physiol, June 1, 2001; 280(6): F1093 - F1106. [Abstract] [Full Text] [PDF]

				H. Velazquez, T. Silva, E. Andujar, G. V. Desir, D. H. Ellison, and R. Greger The distal convoluted tubule of rabbit kidney does not express a functional sodium channel Am J Physiol Renal Physiol, March 1, 2001; 280(3): F530 - F539. [Abstract] [Full Text] [PDF]

				M. Horster Embryonic epithelial membrane transporters Am J Physiol Renal Physiol, December 1, 2000; 279(6): F982 - F996. [Abstract] [Full Text] [PDF]

				R. A. Coleman, D. C. Wu, J. Liu, and J. B. Wade Expression of aquaporins in the renal connecting tubule Am J Physiol Renal Physiol, November 1, 2000; 279(5): F874 - F883. [Abstract] [Full Text] [PDF]

				D. H. Ellison Divalent cation transport by the distal nephron: insights from Bartter's and Gitelman's syndromes Am J Physiol Renal Physiol, October 1, 2000; 279(4): F616 - F625. [Abstract] [Full Text] [PDF]

				J. Loffing, L. Pietri, F. Aregger, M. Bloch-Faure, U. Ziegler, P. Meneton, B. C. Rossier, and B. Kaissling Differential subcellular localization of ENaC subunits in mouse kidney in response to high- and low-Na diets Am J Physiol Renal Physiol, August 1, 2000; 279(2): F252 - F258. [Abstract] [Full Text] [PDF]

				J. Loffing, D. Loffing-Cueni, A. Macher, S. C. Hebert, B. Olson, M. A. Knepper, B. C. Rossier, and B. Kaissling Localization of epithelial sodium channel and aquaporin-2 in rabbit kidney cortex Am J Physiol Renal Physiol, April 1, 2000; 278(4): F530 - F539. [Abstract] [Full Text] [PDF]

				J. Loffing, D. Loffing-Cueni, V. Valderrabano, L. Klausli, S. C. Hebert, B. C. Rossier, J. G. J. Hoenderop, R. J. M. Bindels, and B. Kaissling Distribution of transcellular calcium and sodium transport pathways along mouse distal nephron Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1021 - F1027. [Abstract] [Full Text] [PDF]

				V. Campean, J. Kricke, D. Ellison, F. C. Luft, and S. Bachmann Localization of thiazide-sensitive Na+-Cl- cotransport and associated gene products in mouse DCT Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1028 - F1035. [Abstract] [Full Text] [PDF]