Slit and Robo in Kidney Formation

Science's STKE  18 May 2004:
Vol. 2004, Issue 233, pp. tw176-TW176
DOI: 10.1126/stke.2332004TW176

In a remarkably reliable way, appropriate signals during development guide particular groups of cells to produce intricate organs, such as kidneys, but somehow they don't influence other cells that might make supernumerary organs. Grieshammer et al. implicate in such a process the secreted ligand Slit2 and its receptor Robo2, best known for their role in transmitting chemorepellent signals that guide migration of developing neurons in the central nervous system. Normally, each kidney develops from a single bud (the ureteric bud) that grows from a tubelike structure known as the nephric duct. This budding occurs in response to glial cell line-derived neurotrophic factor (GDNF) that is secreted from adjacent mesenchymal tissue. However, mice lacking the Slit2 gene showed that kidney development was markedly disrupted, and three or more ureteric buds were often formed. Robo2 knockout animals had similar defects, indicating that failure of Slit-Robo signaling accounted for the problem. When Slit was absent, GDNF was produced in a larger area of the nephrogenic mesenchyme, which appeared to explain the extended formation of multiple buds from the nephric duct. The mechanism by which Slit2-Robo2 signaling restricts GDNF expression remains unclear, but it appears to be distinct from the chemorepellent effects for which the pair is most famous. In experiments with transplanted explants, Grieshammer et al. could find no evidence for migration of the GDNF-producing mesenchymal cells that might be regulated by Slit.

U. Grieshammer, L. Ma, A. S. Plump, F. Wang, M. Tessier-Lavigne, G. R. Martin, SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev. Cell 6, 709-717 (2004). [Online Journal]