title: Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors.
abstract: Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a common pool of neural progenitors located in the ventral hindbrain. We found that the temporal specification of these neurons varies along the anterior-posterior axis of the hindbrain, and that the timing of their generation critically depends on the integrated activities of Nkx- and Hox-class homeodomain proteins. A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate. These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Pattyn
authors.forename: Anna
authors.initials: A
authors.lastname: Vallstedt
authors.forename: José M
authors.initials: JM
authors.lastname: Dias
authors.forename: Omar Abdel
authors.initials: OA
authors.lastname: Samad
authors.forename: Robb
authors.initials: R
authors.lastname: Krumlauf
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Rijli
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Brunet
authors.forename: Johan
authors.initials: J
authors.lastname: Ericson
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D019070:Cell Lineage; D002490:Central Nervous System / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins
chemical_list: D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; C490111:Hoxb2 protein, mouse; C109220:NBPhox protein; C436827:Nkx6.2 protein, vertebrate; D014157:Transcription Factors; D029961:Zebrafish Proteins; D001973:Bromodeoxyuridine