The mechanisms of neural abnormalities leading to Down's syndrome and Holoprosencephaly

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07247
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48010:Anatomy-related
• Research Institution: Hiroshima University
• Principal Investigator: Takebayashi-Suzuki Kimiko (鈴木) 広島大学, 両生類研究センター, 研究員 (00397910)
• Co-Investigator(Kenkyū-buntansha): 鈴木 厚 広島大学, 両生類研究センター, 准教授 (20314726)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 神経誘導 / 頭部形成

Outline of Final Research Achievements

The vertebrate body is organized along the dorsal-ventral (DV) and anterior-posterior (AP) axes by the BMP and Wnt pathways, respectively. We previously reported that BMP inhibitory zinc finger (Biz)/Zbtb14 promotes dorsalization (neuralization) of the ectoderm by inhibiting BMP signaling and posteriorizes the induced neural tissue by activating Wnt signaling, thereby coordinating DV and AP patterning during early development.
We found that bap (biz-associated protein) and zbtb14 are co-expressed in the dorsal region of Xenopus embryos during gastrulation. Overexpression of Bap together with Zbtb14 enhanced the activity of Zbtb14 to induce the expression of posterior neural marker genes in ectodermal explants. Moreover, knockdown experiments showed that Bap is required for the formation of posterior neural tissues and the repression of anterior neural development. Collectively, these results suggest that Bap plays an important role in AP patterning during early Xenopus embryogenesis.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

Biz/Zbtb14と結合するBapが、Biz/Zbtb14と協調的に働いて神経誘導を促進する事、およびBapが神経組織の前後軸形成に必要不可欠である事がわかった。興味深いことにヒトのBapはダウン症の原因となる21番染色体の遺伝子であり、ヒトのBapとBiz/Zbtb14は、ともに脳形成異常を示す全前脳胞症の原因遺伝子座に位置する。BapとBiz/Zbtb14は発生初期の神経形成を制御することによって、ダウン症の脳形成不全と全前脳胞症の発症に関与する可能性がある。今後、初期神経発生の知見が豊富なカエル胚を用いて、BapとBiz/Zbtb14の協調作用を詳細に調べるための基盤構築に成功した。