A role of Toll/Irak1: a novel mechanism of head induction

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16138
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Yamamoto Takayoshi 東京大学, 大学院総合文化研究科, 助教 (70724699)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Toll-like receptor / Xenopus / 頭部形成

Outline of Final Research Achievements

The Toll-like receptor pathway (Toll pathway) is essential in innate immune responses, but its role in early vertebrate development was unknown. In this study, we investigated the role of a Toll pathway factor, Irak1. Ectopic expression of Irak1 in Xenopus embryos induced expression of Siamois and Xnr3, target genes of canonical Wnt signaling pathway, and induced head formation. Consistently, Irak1 knockdown partially inhibited head formation. GSK3β expression, which is a component of Wnt pathway, suppressed head induction, but co-injection of Irak1 rescued the phenotype. In contrast, the phenotype when Dishevelled, which functions upstream of GSK3β, was inhibited was not rescued by Irak1. This suggests that Irak1 is required for head formation, and acts at or upstream of Dishevelled in the Wnt pathway.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究ではToll経路からWnt経路に至る新たな分子経路を発見した。これは、発生・自然免疫の基礎的知見として重要である。また免疫系のがん細胞ではToll経路によるWnt経路の活性化が想定されている (Ma and Hottiger, 2016）が、その全貌は未だ不明である。本研究の成果は、このような医学的に重要な現象の分子機構解明につながる可能性を併せ持っており、実用・応用面での波及効果も期待できる。