Mixl1 is required for axial mesendoderm morphogenesis and patterning in the murine embryo.
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.
The Walter and Eliza Hall Institute of Medical Research, P.O. Royal Melbourne Hospital, Vic 3050, Australia.
Adam H
AH
Hart
Lynne
L
Hartley
Koula
K
Sourris
Elizabeth S
ES
Stadler
Ruili
R
Li
Edouard G
EG
Stanley
Patrick P L
PP
Tam
Andrew G
AG
Elefanty
Lorraine
L
Robb
D000818:Animals; D019521:Body Patterning; D004622:Embryo, Mammalian / Q000502:physiology*; D004625:Embryo, Nonmammalian; D005314:Embryonic and Fetal Development; D004707:Endoderm / Q000502:physiology; D005326:Fetal Proteins; D018390:Gene Targeting; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D055457:Nodal Protein; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology; D000098908:Brachyury Protein
D005326:Fetal Proteins; D018398:Homeodomain Proteins; D055457:Nodal Protein; D020825:T-Box Domain Proteins; D016212:Transforming Growth Factor beta; D000098908:Brachyury Protein; C464781:Mixl1 protein, mouse; C526008:Nodal protein, mouse