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EMBRYONIC STEM CELLS

Leukotriene Synthesis Is Required for Hedgehog-Dependent Neurite Projection in Neuralized Embryoid Bodies but Not for Motor Neuron Differentiation

^aCenter for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands;
^bDepartment of Biological Structure, University of Washington, Seattle, Washington, USA;
^cDepartment of Cell Biology, University of Groningen, Groningen, The Netherlands

Key Words. Development • Stem cells • Leukotrienes • Neurons • Cytoskeleton

Correspondence: M.F. Bijlsma, M.Sc., Center for Experimental and Molecular Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Telephone: 0031-0-20-5667062; Fax: 0031-0-20-6977192; e-mail: m.f.bijlsma{at}amc.uva.nl

Received October 4, 2007; accepted for publication February 18, 2008.
First published online in STEM CELLS EXPRESS   February 21, 2008.



The hedgehog (Hh) pathway is required for many developmental processes, as well as for adult homeostasis. Although all known effects of Hh signaling affecting patterning and differentiation are mediated by members of the Gli family of zinc finger transcription factors, we demonstrate that the Hh-dependent formation of neurites from motor neurons, like migration of fibroblasts, requires leukotriene synthesis and is different from the Gli-mediated Hh response. Smoothened activity is required for the use of the leukotriene metabolism, and inversely, the leukotriene metabolism is required for mediating the Hh effects on neurite projection. These data establish a function for the previously described arachidonic acid-dependent Hh pathway in a developmentally relevant model system.

Disclosure of potential conflicts of interest is found at the end of this article.