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The T gene is necessary for normal mesodermal morphogenetic cell movements during gastrulation
V Wilson1, L Manson, W C Skarnes
1Laboratory of Mammalian Development, National Institute for Medical Research, London, UK.
Development (Cambridge, England)
|March 1, 1995
Summary
The T (Brachyury) gene is crucial for mouse embryonic development, particularly primitive streak and notochord formation. Gene deletions lead to abnormal tail development and tissue distribution, impacting posterior axis elongation.
Area of Science:
- Developmental Biology
- Genetics
- Stem Cell Biology
Background:
- The T (Brachyury) gene plays a critical role in mouse embryonic development, specifically in primitive streak and notochord morphogenesis.
- T (Brachyury) gene deletions result in defective posterior axis elongation.
- T/T embryonic stem (ES) cells exhibit abnormal distribution in chimeric embryos, accumulating in the distal tail.
Purpose of the Study:
- To investigate the origin of abnormal tissue distribution of T/T embryonic stem (ES) cells in chimeric mouse embryos.
- To elucidate the role of the T (Brachyury) gene product during gastrulation and its impact on cell behavior.
Main Methods:
- Isolation of T/T and control T/+ ES cell clones using a gene trap strategy for constitutive lacZ expression.
- Visualization of T/T cell distribution in chimeric embryos from gastrulation up to 10.5 days post coitum (dpc).
- Comparison of T expression patterns with T/T cell accumulation sites in developing embryos.
Main Results:
- T/T cells progressively accumulate in the primitive streak during gastrulation and are incorporated into the tailbud.
- Abnormal tail morphology is observed in chimeric embryos at 10.5 dpc, with T/T cells remaining on the surface of the distal tail.
- T/T cells preferentially incorporate into the ventral neural tube and axial mesoderm, leading to fused structures resembling notochordal defects.
Conclusions:
- The T (Brachyury) gene product likely alters cell surface properties, such as adhesion, as cells traverse the primitive streak during gastrulation.
- The aberrant accumulation of T/T cells in the primitive streak prevents posterior neuropore closure, contributing to abnormal tail phenotypes.
- Cell-autonomous changes in adhesion, influenced by T (Brachyury) gene function, may underlie the observed fusion of ventral neural tube and axial mesoderm.