| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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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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