Brn3a regulates the transition from neurogenesis to terminal differentiation and represses non-neural gene expression in the trigeminal ganglion.
The POU-domain transcription factor Brn3a is expressed in developing sensory neurons at all levels of the neural axis, including the trigeminal ganglion, hindbrain sensory ganglia, and dorsal root ganglia. Changes in global gene expression in the trigeminal ganglion from E11.5 to E13.5 reflect the repression of early neurogenic genes, exit from the cell cycle, and initiation of the expression of definitive markers of sensory function. A majority of these developmental changes are perturbed in the trigeminal ganglia of Brn3a knockout mice. At E13.5, Brn3a(-/-) trigeminal neurons fail to repress a battery of developmental regulators that are highly expressed at E11.5 and are normally down-regulated as development progresses, and also fail to appropriately activate a set of definitive sensory genes. Remarkably, developing Brn3a(-/-) trigeminal neurons also ectopically express multiple regulatory genes associated with cardiac and/or cranial mesoderm development, although definitive myogenic programs are not activated. The majority of these genes are not ectopically expressed in the dorsal root ganglia of Brn3a null mice, perhaps due to redundant mechanisms of repression at spinal levels. These results underscore the importance of gene repression in regulating neuronal development, and the need for unbiased screens in the determination of developmental gene regulatory programs.
Lanier
Jason
J
Department of Psychiatry and University of California, San Diego, California 92093-0603, USA.
Dykes
Iain M
IM
Nissen
Stephanie
S
Eng
S Raisa
SR
Turner
Eric E
EE
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D015536:Down-Regulation; D004622:Embryo, Mammalian; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D050437:Genes, Developmental / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology; D050819:Transcription Factor Brn-3A / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000196:embryology* / Q000378:metabolism
C494189:Pou4f1 protein, mouse; D050819:Transcription Factor Brn-3A