Leukotriene Synthesis is Required for Hedgehog-dependent Neurite Projection in Neuralized Embryoid Bodies but not for Motor Neuron Differentiation

¹ Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Biological Structure, University of Washington, Seattle, USA
² Department of Cell Biology, University of Groningen, Groningen, The Netherlands
³ Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands
⁴ Department of Biological Structure, University of Washington, Seattle, USA

^* To whom correspondence should be addressed. E-mail: m.f.bijlsma{at}amc.uva.nl.

	Abstract

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 motorneurons, like migration of fibroblasts, requires leukotriene synthesis and is different from the Gli-mediated Hh response. Smo activity is required for the utilization 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.