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Ectopic expression of the transforming growth factor β type II receptor disrupts mesoderm organisation during mouse gastrulation
Author(s) -
Zwijsen An,
Goumans MarieJosé,
Lawson Kirstie A.,
Van Rooijen Marga A.,
Mummery Christine L.
Publication year - 1999
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/(sici)1097-0177(199902)214:2<141::aid-aja4>3.0.co;2-s
Subject(s) - primitive streak , biology , gastrulation , mesoderm , microbiology and biotechnology , ectopic expression , embryo , embryonic stem cell , transforming growth factor , embryogenesis , medicine , endocrinology , genetics , cell culture , gene
Transforming growth factor β (TGFβ) regulates the cell cycle and extracellular matrix (ECM) deposition of many cells in vitro. We have analysed chimaeric mouse embryos generated from embryonic stem cells with abnormal receptor expression to study the effect of TGFβ on these processes in vivo and the consequences for normal development. The binding receptor for TGFβ, TβRII, is first detected in the embryo proper around day 8.5 in the heart. Ectopic expression of TβRII from the blastocyst stage onward resulted in an embryonic lethal around 9.5 dpc. Analysis of earlier stages revealed that the primitive streak of TβRII chimaeras failed to elongate. Furthermore, although cells passed through the streak and initially formed mesoderm, they tended to accumulate within the streak. These defects temporally and spatially paralleled the expression of the TGFβ type I receptor, which is first expressed in the node and primitive streak. We present evidence that classical TGFβ‐induced growth inhibition was probably the cause of insufficient mesoderm being available for paraxial and axial structures. The results demonstrate that (1) TGFβ mRNA and protein detected previously in early postimplantation embryos is present as a biologically active ligand; and (2) assuming that ectopic expression of TβRII results in no other changes in ES cells, the absence of TβRII is the principle reason why the embryo proper is unresponsive to TGFβ ligand until after gastrulation. Dev Dyn 1999:214:141–151 . © 1999 Wiley‐Liss, Inc.