Origin of anterior-posterior axis in the mouse embryos

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23756
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0702:Biology at cellular to organismal levels, and related fields
• Research Institution: The University of Tokushima
• Principal Investigator: TAKAOKA Katsuyoshi 徳島大学, 先端酵素学研究所, 准教授 (90551044)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: マウス胚 / 前後軸 / 体軸 / 着床 / 非対称性 / 不妊治療 / 体軸 / 子宮

Outline of Final Research Achievements

One fundamental question in developmental biology is how an initially round fertilized egg becomes an elaborately shaped embryo. In Drosophila, whose eggs are elliptical in shape, the anterior-posterior (A-P) axis is specified by asymmetrical distribution of maternal determinants. In mammals such as humans and mice. The A-P axis, the first axis established in mammals, is determined by distal visceral endoderm (DVE). How prospective DVE cells are selected in the embryo, however, has remained unclear. We showed that, in mouse embryos, the DVE is formed through a negative feedback by Lefty1 and Nodal.The DVE then drives the establishment of the A-P axis by migrating to the future anterior side. We made an hypothesis; The DVE cells that determines the anterior-posterior axis direction is produced by the Nodal signals of the ovary, uterus, and embryo acting as a spatiotemporal network, and maternal aging disrupts the patterning of the head-determining cell group AVE.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究は、前後軸の起源を明らかにするという、発生学の本質にアプローチする壮大な研究である。ショウジョウバエを含む多くの生物はすでに卵子の段階で分子レベルの非対称情報を獲得しており、それら分子レベルの非対称情報が後の体軸情報を提供する。それに対して、ヒトやマウスといった胎生動物がいつどのようにして体軸の基となる非対称な分子情報を獲得するのかは長らく不明であり、発生学の命題であった。本研究が完了した場合、発生学の命題が明らかになり、マウス胚発生学の歴史の中で重要なマイルストーンとなる。