2010 Fiscal Year Final Research Report
Role of pioneer neurons in development of peripheral nervous sysytem
| Project/Area Number |
20590177
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | Jichi Medical University |
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Principal Investigator |
IKEDA Keiko Jichi Medical University, 医学部, 准教授 (10265241)
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| Project Period (FY) |
2008 – 2010
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| Keywords | Six遺伝子 / パイオニアニューロン / 末梢神経系 / 嗅上皮発生 / ノックアウトマウス / レチノイン酸 / 組織培養 |
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| Research Abstract |
The olfactory epithelium (OE) is derived from the olfactory placode (OP) during mouse development. At embryonic day (E) 10.0-E10.5, "early neurogenesis" occurs in the OE, which includes production of pioneer neurons that emigrate out of the OE and other early-differentiated neurons. Pioneer neurons migrate out OP/OE and localize between OP/OE and the forebrain. The importance of pioneer neurons are important the first connection between peripheral and central nervous system during the development. To uncover the molecular mechanism that govern this connection, we investigated the genes involved in the production of pioneer neurons using Six1^<-/->, because Six1^<-/-> shows total absence of pioneer neurons and their derivatives. We identified several candidate genes working under Six1. Interestingly, some of them are involved in retinoic acid signaling pathways. Others are genes whose products are important for cell-cell communication, such as Notch and Jagged. In parallel, we found that Six1 is expressed in both apical and basal progenitors at later stages. In Six1^<-/->, apical proliferating cells were absent and no morphologically identifiable sustentacular cells were observed. Consistently, the expression of Notch2 and Jagged1 in the apical layer was absent in Six1^<-/->. Basal proliferating cells were observed in Six1^<-/->, but the expression of Ngn1, NeuroD, Notch1, and Jagged2 in the basal layer was absent. In sum, Six1 regulates the expression of Notch, Jagged, and other neurogenic bHLH transcription factors for production of pioneer neurons, apical progenitors, and basal progenitors.
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