Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors.
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.
Pattyn
Alexandre
A
Department of Cell and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden.
Vallstedt
Anna
A
Dias
José M
JM
Samad
Omar Abdel
OA
Krumlauf
Robb
R
Rijli
Filippo M
FM
Brunet
Jean-Francois
JF
Ericson
Johan
J
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
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