Analysis of positional information and pattern formation in mouse early embryo
Project/Area Number |
18207018
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Developmental biology
|
Research Institution | Kyushu University |
Principal Investigator |
MENO Chikara Kyushu University, Graduate School of Medical Sciences, Professor (20311764)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥49,790,000 (Direct Cost: ¥38,300,000、Indirect Cost: ¥11,490,000)
Fiscal Year 2007: ¥24,050,000 (Direct Cost: ¥18,500,000、Indirect Cost: ¥5,550,000)
Fiscal Year 2006: ¥25,740,000 (Direct Cost: ¥19,800,000、Indirect Cost: ¥5,940,000)
|
Keywords | Left-right axis / anteronosterior axis / Nodal signal / ENU mutagenesis / recessive mutant / 形態異常 / 胚発生 / マウスs |
Research Abstract |
Nodal is a secreted factor belonging to TGFB super-family that directs morphogenesis in the various phases of developmental importance such as the anteroposterior axis, the left-right axis and the primitive streak formation. This project was aimed to understand how these developmental processes were enabled by the regulation of Nodal signal and to create recessive mutant mice with defects in pattern formation. In the anteroposterior formation, tilted expression of Leftyl and Cerl leads to the migration of distal visceral endoderm (DVE). We investigated the origin of this asymmetry by examining Lefty1-LacZ Tg mouse and in situ hybridization, and found that primitive endoderm asymmetrically expressed Leftyl as early as at the stage of implantation Moreover, it has been revealed that this asymmetry could be autonomously generated in the blastocyst, because the expression of Lefty1 was established in the hanging drop culture of blastocyst. In the left-right axis formation, Nodal expression starts in the left lateral plate mesoderm (LPM). To understand the mechanism of initial left-right determination, we made a simulation program that represents a reaction-diffusion of Nodal and lefty. This program was developed on the base of the observations of Nodal and Lefty expression in wild-type embryos, various mouse mutants and embryos subjected to transfection of Nodal or Lefty expression vectors. The simulation could explain the phenotype of various mutants with defects in left-right axis formation Through this analysis, it has been revealed that a reaction -diffusion of Nodal and Lefty amplifies a small difference of gene expression in the node between left and right into "all or nothing" expression of Nodal in the LPM. We also created recessive mutant mice related to pattern formation by ENU mutagenesis in a small scale. We screened 55 lines of G1 and collected various recessive mutants including abnormal left-right axis formation.
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Report
(3 results)
Research Products
(10 results)