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Development 129, 4685-4696 (2002)
Copyright © 2002 The Company of Biologists Limited

Distinct requirements for extra-embryonic and embryonic bone morphogenetic protein 4 in the formation of the node and primitive streak and coordination of left-right asymmetry in the mouse

Takeshi Fujiwara1,*, Deborah B. Dehart2,3, Kathleen K. Sulik2,3 and Brigid L. M. Hogan1,{dagger}

1 Howard Hughes Medical Institute and Department of Cell Biology, Vanderbilt University Medical Center, 1161 21st Ave. South, Nashville, TN 37232-2175
2 Department of Cell and Developmental Biology, The University of North Carolina, Chapel Hill, NC 27599-7178, USA
3 Bowles Center for Alcohol Studies, The University of North Carolina, Chapel Hill, NC 27599-7178, USA
* Present address: Dana-Farber Cancer Institute, Department of Pediatric Oncology, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA

{dagger}Author for correspondence (e-mail: brigid.hogan{at}mcmail.vanderbilt.edu)

Accepted 16 July 2002

In the mouse and chick embryo, the node plays a central role in generating left-right (LR) positional information. Using several different strategies, we provide evidence in the mouse that bone morphogenetic protein 4 (Bmp4) is required independently in two different sites for node morphogenesis and for LR patterning. Bmp4 expression in the trophoblast-derived extra-embryonic ectoderm is essential for the normal formation of the node and primitive streak. However, tetraploid chimera analysis demonstrates that Bmp4 made in epiblast-derived tissues is required for robust LR patterning, even when normal node morphology is restored. In the absence of embryonic Bmp4, the expression of left-side determinants such as Nodal and Lefty2 is absent in the left lateral plate mesoderm (LPM). Noggin-mediated inhibition of Bmp activity in cultured wild-type embryos results in suppression of Nodal expression in the LPM. Thus, unlike previous models proposed in the chick embryo in which Bmp4 suppresses left-sided gene expression, our results suggest that Bmp acts as a positive facilitator of the left-sided molecular cascade and is required for Nodal induction and maintenance in the left LPM.

Key words: Bone morphogenetic protein 4, Mouse, Embryo, LR asymmetry, Node






© The Company of Biologists Ltd 2002