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Neural Tube Closure in Mouse Whole Embryo Culture
Published on: October 21, 2011
Disruption of the talin gene arrests mouse development at the gastrulation stage
S J Monkley1, X H Zhou, S J Kinston
1Department of Biochemistry, University of Leicester, University Road, Leicester, United Kingdom.
Abstract:
Studies on cultured cells show that the cytoskeletal protein talin plays a key role in cell spreading and the assembly of cell-extracellular matrix junctions. To examine the role of talin in vivo, we have generated mice with a targeted disruption of the talin gene. Heterozygotes are normal, but no surviving homozygous mutant animals were obtained, proving that talin is required for embryogenesis. Mutant embryos develop normally to the blastocyst stage and implant, but there is a gross disorganization of the embryos at gastrulation (6.5-7.5 days post coitum), and they die around 8.5-9.5 days post coitum. The embryonic ectoderm is reduced in size, with fewer cells, and is incompletely organised compared with wild-type embryos. The mutant embryos show disorganised extraembryonic tissues, and the ectoplacental and excocoelomic cavities are not formed. This seems to be because embryonic mesoderm accumulates as a mass on the posterior side of the embryos and fails to migrate to extraembryonic regions, although mesodermal cells are evident in the embryo proper. Spreading of trophoblast cells derived from cultured mutant blastocysts on fibronectin and laminin is also considerably reduced. Therefore, the fundamental deficit in these embryos seems to be a failure of cell migration at gastrulation.
Insights
Talin is essential for embryonic development in mice. Gene disruption prevents proper cell migration during gastrulation, leading to embryonic lethality.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- The cytoskeletal protein talin is crucial for cell spreading and cell-extracellular matrix junctions in cultured cells.
- Understanding talin's in vivo function is vital for comprehending its role in development.
Purpose of the Study:
- To investigate the in vivo function of talin during mouse embryogenesis.
- To determine the consequences of talin gene disruption on embryonic development.
Main Methods:
- Generation of mice with a targeted disruption of the talin gene.
- Analysis of homozygous mutant embryos at various developmental stages (up to 8.5-9.5 days post coitum).
- Assessment of cell spreading in cultured trophoblast cells from mutant blastocysts.
Main Results:
- Talin is essential for mouse embryogenesis, as no homozygous mutants survive.
- Mutant embryos exhibit disorganization at gastrulation, with reduced embryonic ectoderm and abnormal extraembryonic tissues.
- Failure of mesoderm migration and reduced trophoblast cell spreading on fibronectin and laminin were observed.
Conclusions:
- Talin plays a critical role in embryonic cell migration during gastrulation.
- Defective cell migration due to talin disruption leads to developmental failure and embryonic lethality.
- Talin is indispensable for the proper formation of embryonic and extraembryonic structures.
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