The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity.
In the vertebrate neural tube, cell cycle exit of neuronal progenitors is accompanied by the expression of transcription factors that define their generic and sub-type specific properties, but how the regulation of cell cycle withdrawal intersects with that of cell fate determination is poorly understood. Here we show by both loss- and gain-of-function experiments that the neuronal-subtype-specific homeodomain transcription factor Phox2b drives progenitor cells to become post-mitotic. In the absence of Phox2b, post-mitotic neuronal precursors are not generated in proper numbers. Conversely, forced expression of Phox2b in the embryonic chick spinal cord drives ventricular zone progenitors to become post-mitotic neurons and to relocate to the mantle layer. In the neurons thus generated, ectopic expression of Phox2b is sufficient to initiate a programme of motor neuronal differentiation characterised by expression of Islet1 and of the cholinergic transmitter phenotype, in line with our previous results showing that Phox2b is an essential determinant of cranial motor neurons. These results suggest that Phox2b coordinates quantitative and qualitative aspects of neurogenesis, thus ensuring that neurons of the correct phenotype are generated in proper numbers at the appropriate times and locations.
Dubreuil
V
V
Laboratoire de Génétique et Physiologie du Développement, IBDM, CNRS-INSERM-Université de la Méditerranée-AP de Marseille, Campus de Luminy case 907, France.
Hirsch
M R
MR
Pattyn
A
A
Brunet
J F
JF
Goridis
C
C
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle; D002465:Cell Movement; D002642:Chick Embryo; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C109220:NBPhox protein; D009419:Nerve Tissue Proteins; C405695:Sh2d3c protein, mouse; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1