Leukotriene synthesis is required for hedgehog-dependent neurite projection in neuralized embryoid bodies but not for motor neuron differentiation.
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.
Bijlsma
Maarten F
MF
Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands. m.f.bijlsma@amc.uva.nl
Peppelenbosch
Maikel P
MP
Spek
C Arnold
CA
Roelink
Henk
H
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053823:Hedgehog Proteins / Q000819:agonists / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D015289:Leukotrienes / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors; D051379:Mice; D009046:Motor Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D016501:Neurites / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011784:Quail; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000072086:Smoothened Receptor; D014404:Tubulin / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1; D002722:Chlorobenzenes
D016718:Arachidonic Acid; D004791:Enzyme Inhibitors; D053823:Hedgehog Proteins; D007211:Indoles; D051741:Kruppel-Like Transcription Factors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D014404:Tubulin; D000071676:Zinc Finger Protein GLI1; C498520:Gli1 protein, mouse; C465570:Shh protein, mouse; C491022:Smo protein, mouse; C462941:beta3 tubulin, mouse; C060893:MK-886; D002722:Chlorobenzenes