title: Engrailed 1 mediates correct formation of limb innervation through two distinct mechanisms.
abstract: Engrailed-1 (En1) is expressed in the ventral ectoderm of the developing limb where it plays an instructive role in the dorsal-ventral patterning of the forelimb. Besides its well-described role as a transcription factor in regulating gene expression through its DNA-binding domain, En1 may also be secreted to form an extracellular gradient, and directly impact on the formation of the retinotectal map. We show here that absence of En1 causes mispatterning of the forelimb and thus defects in the dorsal-ventral pathfinding choice of motor axons in vivo. In addition, En1 but not En2 also has a direct and specific repulsive effect on motor axons of the lateral aspect of the lateral motor column (LMC) but not on medial LMC projections. Moreover, an ectopic dorsal source of En1 pushes lateral LMC axons to the ventral limb in vivo. Thus, En1 controls the establishment of limb innervation through two distinct molecular mechanisms.
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München (GmbH)-German Research Center for Environmental Health, Munich, Germany.
authors.forename: Rosa-Eva
authors.initials: RE
authors.lastname: Huettl
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München (GmbH)-German Research Center for Environmental Health, Munich, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Luxenhofer
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München (GmbH)-German Research Center for Environmental Health, Munich, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bianchi
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München (GmbH)-German Research Center for Environmental Health, Munich, Germany; Institute of Physiology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Haupt
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology, Paris, France.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Joshi
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Prochiantz
authors.affiliation: Institute of Developmental Genetics, Helmholtz Zentrum München (GmbH)-German Research Center for Environmental Health, Munich, Germany.
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Huber
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D004475:Ectoderm / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005552:Forelimb / Q000294:innervation* / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D009046:Motor Neurons / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D036122:Receptor, EphA4 / Q000378:metabolism
chemical_list: C080330:En1 protein, mouse; D018398:Homeodomain Proteins; D036122:Receptor, EphA4