Bone morphogenetic protein 4 signaling regulates development of the anterior visceral endoderm in the mouse embryo

Soares, Miguel Luz; Torres-Padilla, Maria-Elena; Zernicka‐Goetz, Magdalena

doi:10.1111/j.1440-169x.2008.01059.x

Cited by 40 publications

(33 citation statements)

References 25 publications

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“…Cer1-GFP expression becomes localized to the visceral endoderm, when the embryonic fragment (epiblast + visceral endoderm) is cocultured with the posterior extra-embryonic ectoderm, but not with anterior extra-embryonic ectoderm (Richardson et al, 2006). The inhibitory activity of the extra-embryonic ectoderm is diminished by the knockdown of Bmp4 (Soares et al, 2008), indicating that BMP signaling and/or downstream gene activity have a role in this inhibition, which underpins the downregulation of Cer1-GFP in the visceral endoderm outside of the DVE and AVE (Torres-Padilla et al, 2007b). The inhibitory activity of the extra-embryonic ectoderm is expected to diminish with the increase in distance between it and the DVE.…”

Section: Signaling Pathways Establishing the Dve/avementioning

confidence: 99%

Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse

2009

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The investigation into lineage allocation and early asymmetries in the pre-and peri-implantation mouse embryo is gaining momentum. As we review here, new insights have been gained into the cellular and molecular events that lead to the establishment of the three lineages of the blastocyst, to the determination of the origin and the fates of the visceral endoderm in the peri-implantation mouse embryo, and to the generation of cellular and molecular activities that accompany the emergence of asymmetries in the pre-gastrulation embryo. We also discuss the continuing debate that surrounds the relative impacts of early lineage bias versus the stochastic allocation of cells with respect to the events that pattern the blastocyst and initiate its later asymmetries. IntroductionThe progression of the mammalian embryo from fertilization to gastrulation involves an ordered series of lineage specifications and axial asymmetries (Fig. 1) that result, first, in the development of the blastocyst (see Glossary, Box 1), with its embryonic-abembryonic axis ( Fig. 1; Box 2), and, later, in the formation of the embryo itself, with its anterior-posterior (AP), dorsal-ventral (DV) and left-right (LR) axes. In many invertebrates and vertebrates, asymmetries that are established in the egg correlate with the segregation of determinants that influence later lineage formation and axis development. However, in the mouse egg, the morphological asymmetries that exist, such as the position of the second polar body (see Glossary, Box 1) and the sperm entry point, do not clearly demarcate an asymmetric domain of, for example, signaling activity or of cell fate determinants in the fertilized mouse egg. Whether there is any instructive relationship between the asymmetry of the egg and the later asymmetry of the blastocyst and lineage allocation remains a controversial issue. It is well known that the pre-implantation mammalian embryo is highly regulative and resistant to the loss or addition of cells brought about by experimental manipulations. However, this does not preclude the existence of an, as yet, uncharacterized property that could bias developmental outcomes in the intact embryo.Whether any early asymmetries in the mouse egg and/or blastocyst relate to the orientation of the definitive body axes is even less certain. It is now clear that the AP patterning of the gastrulating embryo is initiated prior to gastrulation by spatially localized signals that emanate from regionally patterned extra-embryonic tissues. Some of these asymmetries may be set up as early as the blastocyst stage, linking pre-implantation patterning to post-implantation morphogenesis.Here, we review recent experiments that define the molecular components of lineage specification in the mouse blastocyst. We also review the ongoing uncertainty and debate that surrounds the relative importance of early cleavage patterns at the two-to four-cell stage and of symmetric versus asymmetric divisions at the eight-to 16-and 16-to 32-cell stage, and the importance of final cell po...

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Section: Signaling Pathways Establishing the Dve/avementioning

confidence: 99%

Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse

2009

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“…1B) (Mellitzer et al, 2002;Soares et al, 2008). However, it can be inferred from computations of the electric potential at the surface of an ellipsoid model that although permeation localisation is optimal when the longer axis of the embryo is perpendicular to both electrodes, it degrades as soon as a tilt angle exists, becoming nearly impossible after a 90°rotation (Valic et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

“…A variety of molecules can be efficiently introduced into cells by electroporation, including DNA, mRNA (Cerda et al, 2006;Chernet and Levin, 2012), dsRNA (Mellitzer et al, 2002;Soares et al, 2008), morpholinos (Falk et al, 2007;Mellitzer et al, 2002;Voiculescu et al, 2008), siRNA (Calegari et al, 2004;Paganin-Gioanni et al, 2011), proteins and drugs (Teissie et al, 2012). In this work we concentrated on DNA electroporation to provide a readout for transfection.…”

Section: Discussionmentioning

confidence: 99%

“…This approach has been implemented most successfully when the tissue of interest surrounds a natural body cavity in which microinjection is possible, for example the neural tube lumen or the proamniotic cavity of vertebrate embryos (Itasaki et al, 1999;Soares et al, 2008). In other situations, such as experiments involving epithelial tissues lying at the periphery of embryos or organs, the geometry and the position of the targeted area do not allow local concentration of the exogenous molecule.…”

Section: Introductionmentioning

confidence: 99%

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A microdevice to locally electroporate embryos with high efficiency and reduced cell damage

et al. 2014

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The ability to follow and modify cell behaviour with accurate spatiotemporal resolution is a prerequisite to study morphogenesis in developing organisms. Electroporation, the delivery of exogenous molecules into targeted cell populations through electric permeation of the plasma membrane, has been used with this aim in different model systems. However, current localised electroporation strategies suffer from insufficient reproducibility and mediocre survival when applied to small and delicate organisms such as early post-implantation mouse embryos. We introduce here a microdevice to achieve localised electroporation with high efficiency and reduced cell damage. In silico simulations using a simple electrical model of mouse embryos indicated that a dielectric guide-based design would improve on existing alternatives. Such a device was microfabricated and its capacities tested by targeting the distal visceral endoderm (DVE), a migrating cell population essential for anterior-posterior axis establishment. Transfection was efficiently and reproducibly restricted to fewer than four visceral endoderm cells without compromising cell behaviour and embryo survival. Combining targeted mosaic expression of fluorescent markers with live imaging in transgenic embryos revealed that, like leading DVE cells, non-leading ones send long basal projections and intercalate during their migration. Finally, we show that the use of our microsystem can be extended to a variety of embryological contexts, from preimplantation stages to organ explants. Hence, we have experimentally validated an approach delivering a tailor-made tool for the study of morphogenesis in the mouse embryo. Furthermore, we have delineated a comprehensive strategy for the development of ad hoc electroporation devices.

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“…de crescimento e proteinases de invasão (Soares et al, 2008;Mas et al, 2008;Simón, Valbuena, 1999;Rogers, Harper 1992;Murphy, 1989;).…”

Section: Introductionunclassified

O impacto da exposição pré-gestacional à poluição atmosférica sobre o processo de implantação embrionária em camundongos

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Bone morphogenetic protein 4 signaling regulates development of the anterior visceral endoderm in the mouse embryo

Cited by 40 publications

References 25 publications

Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse

Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse

A microdevice to locally electroporate embryos with high efficiency and reduced cell damage

O impacto da exposição pré-gestacional à poluição atmosférica sobre o processo de implantação embrionária em camundongos

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