Coordinated regulation of gene expression by Brn3a in developing sensory ganglia.
Mice lacking the POU-domain transcription factor Brn3a exhibit marked defects in sensory axon growth and abnormal sensory apoptosis. We have determined the regulatory targets of Brn3a in the developing trigeminal ganglion using microarray analysis of Brn3a mutant mice. These results show that Brn3 mediates the coordinated expression of neurotransmitter systems, ion channels, structural components of axons and inter- and intracellular signaling systems. Loss of Brn3a also results in the ectopic expression of transcription factors normally detected in earlier developmental stages and in other areas of the nervous system. Target gene expression is normal in heterozygous mice, consistent with prior work showing that autoregulation by Brn3a results in gene dosage compensation. Detailed examination of the expression of several of these downstream genes reveals that the regulatory role of Brn3a in the trigeminal ganglion appears to be conserved in more posterior sensory ganglia but not in the CNS neurons that express this factor.
Eng
S Raisa
SR
Department of Psychiatry, University of California, San Diego, and the VA San Diego Healthcare System, La Jolla, CA 92093-0603, USA.
Lanier
Jason
J
Fedtsova
Natalia
N
Turner
Eric E
EE
D000818:Animals; D064032:Calbindin 2; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000196:embryology*
D064032:Calbindin 2; D004268:DNA-Binding Proteins; D018377:Neurotransmitter Agents; C494189:Pou4f1 protein, mouse; D064030:S100 Calcium Binding Protein G; D013002:Somatomedins; D050818:Transcription Factor Brn-3; D050819:Transcription Factor Brn-3A; D014157:Transcription Factors