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1 Division of Nephrology, Department of Medicine, Vanderbilt Medical Center, Nashville, TN, USA
2 Department of Pathology, Vanderbilt Medical Center, Nashville, TN, USA
3 Department of Medicine and Pediatrics, University of California, San Diego, San Diego, CA, USA
4 Department of Medicine, Children's Hospital, Harvard Medical School, Boston, MA, USA
5 Medical Biochemistry Laboratory and the Department of Biochemistry, University of Turku, Turku, Finland
6 Division of Nephrology, Department of Medicine, Vanderbilt Medical Center, Nashville, TN, USA; Veterans Affairs Hosptial, Nashville, TN, USA
7 Division of Nephrology, Department of Medicine, Vanderbilt Medical Center, Nashville, TN, USA; Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA; Veterans Affairs Hosptial, Nashville, TN, USA
* To whom correspondence should be addressed. E-mail: roy.zent{at}vanderbilt.edu.
Inner medullary collecting ducts (IMCD) are terminally differentiated structures derived from the ureteric bud (UB). UB development is mediated by changes in the temporal and spatial expression of integrins and their respective ligands. We demonstrate both in vivo and in vitro
that the UB expresses predominantly laminin receptors (integrins 
3
1, 61 and 64), while the IMCD expresses both collagen (integrins 11 and 21) and laminin receptors. Cells derived from the IMCD, but not the UB, undergo tubulogenesis in collagen-I (CI) gels in a 11- and 21-dependent manner. UB cells transfected with the 2 integrin subunit undergo tubulogenesis in CI, suggesting that collagen receptors are required for branching morphogenesis in CI. In contrast, both UB and IMCD cells undergo tubulogenesis in CI/Matrigel (MG) gels. UB
cells primarily utilize 31 and 6 integrins, while IMCD cells mainly employ 11 for this process. These results demonstrate a switch in integrin expression from primarily laminin receptors in the early UB to both collagen and laminin receptors in the mature IMCD, which has functional consequences for branching morphogenesis in 3D cell culture models. This suggests that temporal and spatial changes in integrin expression could help organize the pattern of branching morphogenesis of the developing collecting system in vivo.
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