title: An early role for WNT signaling in specifying neural patterns of Cdx and Hox gene expression and motor neuron subtype identity.
abstract: The link between extrinsic signaling, progenitor cell specification and neuronal subtype identity is central to the developmental organization of the vertebrate central nervous system. In the hindbrain and spinal cord, distinctions in the rostrocaudal identity of progenitor cells are associated with the generation of different motor neuron subtypes. Two fundamental classes of motor neurons, those with dorsal (dMN) and ventral (vMN) exit points, are generated over largely non-overlapping rostrocaudal domains of the caudal neural tube. Cdx and Hox genes are important determinants of the rostrocaudal identity of neural progenitor cells, but the link between early patterning signals, neural Cdx and Hox gene expression, and the generation of dMN and vMN subtypes, is unclear. Using an in vitro assay of neural differentiation, we provide evidence that an early Wnt-based program is required to interact with a later retinoic acid- and fibroblast growth factor-mediated mechanism to generate a pattern of Cdx and Hox profiles characteristic of hindbrain and spinal cord progenitor cells that prefigure the generation of vMNs and dMNs.
authors.affiliation: 1Umeå Center for Molecular Medicine, Umeå University, Umeå, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Nordström
authors.forename: Esther
authors.initials: E
authors.lastname: Maier
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Jessell
authors.forename: Thomas
authors.initials: T
authors.lastname: Edlund
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology*; D002642:Chick Embryo; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D030161:Avian Proteins; D018398:Homeodomain Proteins; D020825:T-Box Domain Proteins; D051153:Wnt Proteins; D014212:Tretinoin; D005346:Fibroblast Growth Factors