Differential expression of collagen- and laminin-binding integrins mediates ureteric bud and inner medullary collecting duct cell tubulogenesis.
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 (alpha3beta1-, alpha6beta1-, and alpha6beta(4-integrins), whereas the IMCD expresses both collagen (alpha1beta1- and alpha2beta1-integrins) and laminin receptors. Cells derived from the IMCD, but not the UB, undergo tubulogenesis in collagen-I (CI) gels in an alpha1beta1- and alpha2beta1-dependent manner. UB cells transfected with the alpha2-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 gels. UB cells primarily utilize alpha3beta1- and alpha6-integrins, whereas IMCD cells mainly employ alpha1beta1 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 three-dimensional 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.
Chen
Dong
D
Division of Nephrology, Department of Medicine, Vanderbilt Medical Center, Nashville, Tennessee 37232, USA.
Roberts
Richard
R
Pohl
Martin
M
Nigam
Sanjay
S
Kreidberg
Jordan
J
Wang
Zemin
Z
Heino
Jyrki
J
Ivaska
Johanna
J
Coffa
Sergio
S
Harris
Raymond C
RC
Pozzi
Ambra
A
Zent
Roy
R
D000818:Animals; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000502:physiology; D003094:Collagen / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D039222:Integrin alpha1beta1 / Q000235:genetics* / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000235:genetics* / Q000378:metabolism; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism; D039121:Integrin alpha6beta1 / Q000235:genetics / Q000378:metabolism; D039161:Integrin alpha6beta4 / Q000235:genetics / Q000378:metabolism; D007679:Kidney Medulla / Q000166:cytology / Q000196:embryology / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000196:embryology / Q000502:physiology; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D014513:Ureter / Q000196:embryology* / Q000502:physiology*
D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D039201:Integrin alpha3beta1; D039121:Integrin alpha6beta1; D039161:Integrin alpha6beta4; D007797:Laminin; D003094:Collagen