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Am J Physiol Renal Physiol 286: F625-F633, 2004. First published December 2, 2003; doi:10.1152/ajprenal.00152.2003
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Smad expression during kidney development

P. Vrljicak,1,2 D. Myburgh,1 A. K. Ryan,1,2 M. A. van Rooijen,3 C. L. Mummery,3 and I. R. Gupta1,2

Departments of 1Pediatrics and 2Human Genetics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada H3H 1P3; and 3Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands

Submitted 18 April 2003 ; accepted in final form 25 November 2003

Signaling by the transforming growth factor (TGF)-{beta} superfamily is important during kidney development. Here, we describe the spatial and temporal expression patterns of the Smads, the transcription factors that translate TGF-{beta} signals into gene expression. RT-PCR data and in situ hybridization analysis showed that the receptor-regulated (R) Smads (Smad1, -2, -3, -5, and -8), the common partner Smad (Smad4), and the inhibitory (I) Smads (Smad6 and -7) were all expressed during mouse kidney development from embryonic day 12 until the end of nephrogenesis at postnatal day 15. Each Smad had a distinct spatial distribution. All were expressed by mesenchymal cells in the nephrogenic zone and were downregulated once these cells began to epithelialize. The common partner Smad, Smad4, was present in uninduced mesenchymal cells and at ureteric bud tips. The bone morphogenetic-responsive R-Smads, Smad1, -5, and -8, were mainly expressed in the nephrogenic zone, whereas the TGF-{beta}- responsive R-Smads were predominantly noted in the medullary interstitium. Expression of the I-Smad Smad7 was also seen in mesenchymal cells in the interstitium. Based on the observed patterns of expression, we speculate that individual or combinations of Smads may play specific roles in cell-fate determination during kidney development.

transforming growth factor-{beta} signaling; mRNA


Address for reprint requests and other correspondence: I. R. Gupta, Montreal Children's Hospital, 2300 Tupper St., Montreal, Quebec, Canada H3H 1P3 (E-mail: indra.gupta{at}muhc.mcgill.ca).




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