A novel role for the chemokine receptor Cxcr4 in kidney morphogenesis: an in vitro study.
The CXCR4 chemokine receptor is involved in hematopoietic stem cell homing, neuronal development, and angiogenesis. We show a significant new role for this receptor in epithelial patterning and renal morphogenesis. This receptor is expressed in the ureteric bud (UB) and the metanephric mesenchyme (MM). Stimulation of Cxcr4 in renal tubular cells leads to activation of multiple signaling pathways and tubulogenesis and cell migration. Knocking down of this receptor in tubular cells leads to cyst formation. Inactivation of this receptor in embryonic kidney explants results in impaired UB branching and mesenchymal tubulogenesis. The data presented here point to its importance in the process of mesenchymal-to-epithelial transitioning (MET), a crucial developmental process in the embryonic kidney. A number of genes important for normal tubulogenesis and MET are decreased upon CXCR4 inactivation.
Ueland
Joseph
J
Department of Internal Medicine, Section of Nephrology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Yuan
Amy
A
Marlier
Arnaud
A
Gallagher
Anna Rachel
AR
Karihaloo
Anil
A
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D055785:Gene Knockdown Techniques; D007684:Kidney Tubules / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis / Q000235:genetics; D009924:Organ Culture Techniques; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology*
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4