Slit and Robo in Kidney Formation

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Science  28 May 2004:
Vol. 304, Issue 5675, pp. 1215
DOI: 10.1126/science.304.5675.1215c

During development appropriate signals guide particular groups of cells to produce intricate organs, such as kidneys, but somehow don't influence other cells that might make supernumerary organs. 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-derived neurotrophic factor (GDNF) secreted from adjacent mesenchymal tissue. The secreted ligand, Slit2, and its receptor, Robo2, are best known for their role in transmitting chemorepellent signals that guide migration of developing neurons. Grieshammer et al. now find that in mice lacking the Slit2 gene kidney development is disrupted, and three or more ureteric buds are 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 may explain the extended formation of multiple buds from the nephric duct. The mechanism by which Slit2-Robo2 signaling restricts GDNF expression remains unclear, but appears to be distinct from that underlying the known chemorepellent effects. — LBR

Dev. Cell 6, 709 (2004).

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