Six1 and Six4 promote survival of sensory neurons during early trigeminal gangliogenesis.
Survival of sensory neurons is tightly regulated in cell-type and developmental-stage-specific manners. The transcriptional regulatory mechanisms underlying this regulation remain to be elucidated. In the present study, we investigated the role of Six1 and Six4 in the development of trigeminal ganglia. Abundant expression of Six1 and Six4 was noted in sensory neurons during early trigeminal gangliogenesis. Loss of both Six1 and Six4 in mice caused severe defects in the trigeminal ganglia, wherein massive apoptosis accompanied by activation of caspase-3 was observed at early but not late stages of gangliogenesis. In Six1(-/-)Six4(-/-) mice, trigeminal sensory neurons were generated, but showed reduced expression of Bcl-x compared with the wild-type mice. Accordingly, neurons from the deficient mice could not survive in culture even in the presence of neurotrophins. Our results suggest a cell-intrinsic role of Six1 and Six4 in the survival of early-generated trigeminal sensory neurons.
Konishi
Yoshiyuki
Y
Division of Biology Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
Ikeda
Keiko
K
Iwakura
Yoichiro
Y
Kawakami
Kiyoshi
K
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism
D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; C490947:Six1 protein, mouse; C497420:Six2 protein, mouse; D014157:Transcription Factors