Mixl1 is required for axial mesendoderm morphogenesis and patterning in the murine embryo
Abstract
In Xenopus, the Mix/Bix family of homeobox genes has been implicated in mesendoderm development. Mixl1 is the only known murine member of this family. To examine the role of Mixl1 in murine embryogenesis, we used gene targeting to create mice bearing a null mutation of Mixl1. Homozygous Mixl1 mutant embryos can be distinguished from their littermates by a marked thickening of the primitive streak. By the early somite stage, embryonic development is arrested, with the formation of abnormal head folds, foreshortened body axis, absence of heart tube and gut, deficient paraxial mesoderm, and an enlarged midline tissue mass that replaces the notochord. Development of extra-embryonic structures is generally normal except that the allantois is often disproportionately large for the size of the mutant embryo. In chimeras, Mixl1–/– mutant cells can contribute to all embryonic structures, with the exception of the hindgut, suggesting that Mixl1 activity is most crucial for endodermal differentiation. Mixl1 is therefore required for the morphogenesis of axial mesoderm, the heart and the gut during embryogenesis.
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Many key genes involved in the initial formation of DE are evolutionarily conserved.
“Many of the key genes involved in the initial formation of DE are evolutionarily conserved.”
From A systematic screen for genes expressed in definitive endoderm by Serial Analysis of Gene Expression (SAGE) (2007) · cites this paper as [8]
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- Authors
- Hart, A. H., Hartley, L., Sourris, K., Stadler, E. S., Li, R., Stanley, E. G., Tam, P. P. L., Elefanty, A. G., & Robb, L.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Children's Medical Research Institute (AU)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2002-08-01
- Volume
- 129
- Issue
- 15
- Pages
- 3597-3608
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2188419093
- Cited by
- 229
- References
- 68
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 6 · 2023: 10 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 7 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 13 · 2014: 11 · 2013: 9 · 2012: 12
- FWCI
- 2.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- Mixl1, primitive streak, heart development, intestinal development, endoderm differentiation, paraxial mesoderm, notochord, allantois, embryonic lethality, chimeras, mouse embryo
- MeSH terms
- Brachyury Protein, Animals, Embryo, Mammalian, Embryo, Nonmammalian, Endoderm, Embryonic and Fetal Development, Fetal Proteins, Mesoderm, Morphogenesis, Stem Cells, Zebrafish, Signal Transduction, Transforming Growth Factor beta, In Situ Hybridization, Genes, Reporter, Mice, Knockout, Gene Targeting, Homeodomain Proteins, Body Patterning, T-Box Domain Proteins, Mice, Nodal Protein
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