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Publication : The role of the brachyury gene in heart development and left-right specification in the mouse.

First Author  King T Year  1998
Journal  Mech Dev Volume  79
Issue  1-2 Pages  29-37
PubMed ID  10349618 Mgi Jnum  J:52218
Mgi Id  MGI:1328649 Doi  10.1016/s0925-4773(98)00166-x
Citation  King T, et al. (1998) The role of the brachyury gene in heart development and left-right specification in the mouse. Mech Dev 79(1-2):29-37
abstractText  The midline has a theoretical role in the development of left-right asymmetry, and this is supported by both genetic analyses and experimental manipulation of midline structures in vertebrates. The mouse brachyury gene encodes a transcription factor which is expressed in the developing notochord and is required for its development. T/T mice lack a mature notochord and have a dorsalised neural tube. We have examined the hearts of T/T mice and have found consistent morphological abnormalities, resulting in ventrally displaced ventricular loops, and a 50% incidence of inverted heart situs. Three TGF-beta related genes, lefty-1, lefty-2 and nodal, are expressed asymmetrically in mouse embryos, and are implicated in the development of situs. We find that nodal, which is normally expressed around the node and in left lateral plate mesoderm in early somite embryos, is completely absent at this stage in T/T embryos. In contrast, lefty-1 and lefty-2, which are normally expressed in the left half of prospective floorplate and left lateral plate mesoderm, respectively, are both expressed in T/T-embryos only in a broad parch of ventral cells in, and just rostral to, the node region. These results implicate the node as a source of instructive signals driving expression of nodal and lefty-2 in the left lateral plate mesoderm, and being required for normal looping and situs of the heart. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
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