Pax-3 regulates neurogenesis in neural crest-derived precursor cells.
The peripheral nervous system consists of multiple neural lineages derived from the neural crest (NC). Pax-3 is expressed in the NC and when mutated in the splotch mouse (Sp) results in the loss of derivatives from this precursor cell population. We have investigated the role of Pax-3 in regulating the generation of neurons from NC-derived precursor cells in vitro. Pax-3 mRNA in NC cultures is initially expressed in all NC but is subsequently only retained in neurons, suggesting a role in their generation. To determine whether Pax-3 is involved in neuron development, we first examined the generation of sensory-like neurons in NC cultures from Sp mice. Fivefold less sensory-like neurons were generated in NC cultures from Sp homozygous mice as compared to wild-type littermates. The role of Pax-3 in sensory neuron generation was then directly examined in dorsal root ganglia cultures by down-regulating the expression of Pax-3 protein with antisense oligonucleotides. It was found that antisense oligonucleotides inhibited 80-90% of newly generated sensory neurons; however, there was no significant effect on the survival of sensory neurons or the precursor population. These results suggest that Pax-3 has a role in regulating the differentiation of peripheral neurons.
Koblar
S A
SA
The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria, Australia.
Murphy
M
M
Barrett
G L
GL
Underhill
A
A
Gros
P
P
Bartlett
P F
PF
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005838:Genotype; D051379:Mice; D008808:Mice, Inbred CBA; D008818:Mice, Neurologic Mutants; D009432:Neural Crest / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D013873:Thionucleotides; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D013873:Thionucleotides; D014157:Transcription Factors; C068686:Pax3 protein, mouse