title: A local source of FGF initiates development of the unmyelinated lineage of sensory neurons.
abstract: The principle by which unmyelinated primary sensory neurons transducing thermal, itch and pain perception are specified in early development is unknown. These classes of sensory neurons diversify from a common population of late-born neurons, which initiate expression of Runt homology domain transcription factor RUNX1 and the nerve growth factor receptor TrkA. Here, we report that signals emanating from within the mouse dorsal root ganglion mediated partly by early-born neurons destined to a myelinated phenotype participate in fating late-born RUNX1(+)/TrkA(+) neurons. Inductive factors include FGFs via activation of FGF receptor 1 (FGFR1). Consistently, FGF2 is sufficient to induce expression of RUNX1, and Fgfr1 conditional mutant mice display deficits in fating of the common population of late-born RUNX1(+)/TrkA(+) neurons that develop into unmyelinated neurons. Thus, the distinct lineages of sensory neurons are acquired in response to increasing FGF levels provided by a rising number of born neurons.
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics and Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden, and Stellenbosch Institute for Advanced Study, Wallenberg Research Center at Stellenbosch University, Stellenbosch 7600, South Africa.
authors.forename: Saïda
authors.initials: S
authors.lastname: Hadjab
authors.forename: Marina C M
authors.initials: MC
authors.lastname: Franck
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Wang
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sterzenbach
authors.forename: Anil
authors.initials: A
authors.lastname: Sharma
authors.forename: Patrik
authors.initials: P
authors.lastname: Ernfors
authors.forename: Francois
authors.initials: F
authors.lastname: Lallemend
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000502:physiology*; D002642:Chick Embryo; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism / Q000502:physiology*; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D005346:Fibroblast Growth Factors; D020917:Receptor, trkA