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Am J Physiol Renal Physiol (December 2, 2003). doi:10.1152/ajprenal.00152.2003
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Submitted on April 18, 2003
Accepted on November 25, 2003

Smad Expression during Kidney Development

P. Vrljicak1, D. Myburgh2, A. K. Ryan1, M. A. van Rooijen3, C. L. Mummery3, and I. R. Gupta1*

1 Department of Pediatrics, Montreal Children's Hospital, Montreal, Quebec, Canada; Department of Human Genetics, McGill University, Montreal, Quebec, Canada
2 Department of Pediatrics, Montreal Children's Hospital, Montreal, Quebec, Canada
3 Netherlands Institute for Developmental Biology, Hubrecht Laboratory, Utrecht, Netherlands Antilles

* To whom correspondence should be addressed. E-mail: indra.gupta{at}muhc.mcgill.ca.

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 receptorregulated (R) Smads (Smads1, -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, Smads1, -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 inhibitory 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.




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