Expression of Phox2 transcription factors and induction of the dopaminergic phenotype in primary sensory neurons.
Cell-type-specific transcription factors may regulate phenotypic diversity by conferring selective responsiveness to relatively nonspecific environmental cues. To test this hypothesis, we examined whether the homeodomain transcription factors Phox2a/2b play a role in activity-dependent expression of the dopaminergic phenotype using petrosal ganglion (PG) sensory neurons as a model. The timing of Phox2a/2b expression is precisely correlated with the ability of PG neurons to express the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), in response to depolarizing stimuli. Phox2a/2b expression is highest at embryonic day 16.5, when virtually all PG neurons exhibit activity-dependent TH induction, and subsequently falls in parallel with the loss of activity-dependent TH induction. Expression is maintained, however, in all dopaminergic neurons. Physiologic stimulation of PG neurons in vivo induces TH expression exclusively in Phox2a/2b(+) cells. Our data suggest that constitutive expression of Phox2a/2b defines the potential of neurons to become dopaminergic in response to membrane depolarization during a critical window of phenotypic plasticity.
Brosenitsch
Teresa A
TA
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Katz
David M
DM
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004298:Dopamine / Q000096:biosynthesis*; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000096:biosynthesis*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C100935:Phox2a protein, rat; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine