title: Uncoupling of molecular maturation from peripheral target innervation in nociceptors expressing a chimeric TrkA/TrkC receptor.
abstract: Neurotrophins and their receptors control a number of cellular processes, such as survival, gene expression and axonal growth, by activating multiple signalling pathways in peripheral neurons. Whether each of these pathways controls a distinct developmental process remains unknown. Here we describe a novel knock-in mouse model expressing a chimeric TrkA/TrkC (TrkAC) receptor from TrkA locus. In these mice, prospective nociceptors survived, segregated into appropriate peptidergic and nonpeptidergic subsets, projected normally to distinct laminae of the dorsal spinal cord, but displayed aberrant peripheral target innervation. This study provides the first in vivo evidence that intracellular parts of different Trk receptors are interchangeable to promote survival and maturation of nociceptors and shows that these developmental processes can be uncoupled from peripheral target innervation. Moreover, adult homozygous TrkAC knock-in mice displayed severe deficits in acute and tissue injury-induced pain, representing the first viable adult Trk mouse mutant with a pain phenotype.
authors: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, Marseille, France.
authors: Svetlana
authors: S
authors: Gorokhova
authors: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, Marseille, France.
authors: Stéphane
authors: S
authors: Gaillard
authors: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, Marseille, France.
authors: Louise
authors: L
authors: Urien
authors: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, Marseille, France.
authors: Pascale
authors: P
authors: Malapert
authors: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, Marseille, France.
authors: Wassim
authors: W
authors: Legha
authors: MGX-Montpellier GenomiX, c/o Institut de Génomique Fonctionnelle, Montpellier, France.
authors: Grégory
authors: G
authors: Baronian
authors: MGX-Montpellier GenomiX, c/o Institut de Génomique Fonctionnelle, Montpellier, France.
authors: Jean-Pierre
authors: JP
authors: Desvignes
authors: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, Marseille, France.
authors: Serge
authors: S
authors: Alonso
authors: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, Marseille, France.
authors: Aziz
authors: A
authors: Moqrich
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D055879:Gene Knock-In Techniques; D051379:Mice; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D009619:Nociceptors; D010146:Pain / Q000235:genetics* / Q000473:pathology; D020917:Receptor, trkA / Q000235:genetics*; D020812:Receptor, trkC / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000254:growth & development* / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D020917:Receptor, trkA; D020812:Receptor, trkC