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1.
Nat Commun ; 12(1): 3277, 2021 06 02.
Article in English | MEDLINE | ID: mdl-34078907

ABSTRACT

Generating properly differentiated embryonic structures in vitro from pluripotent stem cells remains a challenge. Here we show that instruction of aggregates of mouse embryonic stem cells with an experimentally engineered morphogen signalling centre, that functions as an organizer, results in the development of embryo-like entities (embryoids). In situ hybridization, immunolabelling, cell tracking and transcriptomic analyses show that these embryoids form the three germ layers through a gastrulation process and that they exhibit a wide range of developmental structures, highly similar to neurula-stage mouse embryos. Embryoids are organized around an axial chordamesoderm, with a dorsal neural plate that displays histological properties similar to the murine embryo neuroepithelium and that folds into a neural tube patterned antero-posteriorly from the posterior midbrain to the tip of the tail. Lateral to the chordamesoderm, embryoids display somitic and intermediate mesoderm, with beating cardiac tissue anteriorly and formation of a vasculature network. Ventrally, embryoids differentiate a primitive gut tube, which is patterned both antero-posteriorly and dorso-ventrally. Altogether, embryoids provide an in vitro model of mammalian embryo that displays extensive development of germ layer derivatives and that promises to be a powerful tool for in vitro studies and disease modelling.


Subject(s)
Body Patterning/genetics , Embryoid Bodies/metabolism , Embryonic Development/genetics , Mouse Embryonic Stem Cells/metabolism , Signal Transduction/genetics , Animals , Ectoderm/cytology , Ectoderm/growth & development , Ectoderm/metabolism , Embryo, Mammalian , Embryoid Bodies/cytology , Endoderm/cytology , Endoderm/growth & development , Endoderm/metabolism , GATA6 Transcription Factor/genetics , GATA6 Transcription Factor/metabolism , Gastrula/cytology , Gastrula/growth & development , Gastrula/metabolism , Gastrulation/genetics , Gene Expression Regulation, Developmental , HMGB Proteins/genetics , HMGB Proteins/metabolism , Mice , Mouse Embryonic Stem Cells/cytology , Nanog Homeobox Protein/genetics , Nanog Homeobox Protein/metabolism , Neural Tube/cytology , Neural Tube/growth & development , Neural Tube/metabolism , Notochord/cytology , Notochord/growth & development , Notochord/metabolism , SOXF Transcription Factors/genetics , SOXF Transcription Factors/metabolism
2.
Dev Dyn ; 250(2): 249-262, 2021 02.
Article in English | MEDLINE | ID: mdl-32562595

ABSTRACT

BACKGROUND: During embryonic development, complex changes in cell behavior generate the final form of the tissues. Extension of cell protrusions have been described as an important component in this process. Cellular protrusions have been associated with generation of traction, intercellular communication or establishment of signaling gradients. Here, we describe and compare in detail from live imaging data the dynamics of protrusions in the surface ectoderm of chick and mouse embryos. In particular, we explore the differences between cells surrounding the lens placode and other regions of the head. RESULTS: Our results showed that protrusions from the eye region in mouse embryos are longer than those in chick embryos. In addition, protrusions from regions where there are no significant changes in tissue shape are longer and more stable than protrusions that surround the invaginating lens placode. We did not find a clear directionality to the protrusions in any region. Finally, we observed intercellular trafficking of membrane puncta in the protrusions of both embryos in all the regions analyzed. CONCLUSIONS: In summary, the results presented here suggest that the dynamics of these protrusions adapt to their surroundings and possibly contribute to intercellular communication in embryonic cephalic epithelia.


Subject(s)
Cell Surface Extensions , Ectoderm/cytology , Animals , Chick Embryo , Mice , Morphogenesis
3.
Int J Dev Biol ; 65(4-5-6): 235-244, 2021.
Article in English | MEDLINE | ID: mdl-32930358

ABSTRACT

For over 100 years, the vertebrate eye has been an important model system to understand cell induction, cell shape change, and morphogenesis during development. In the past, most of the studies examined histological changes to detect the presence of induction mechanisms, but the advancement of molecular biology techniques has made exploring the genetic mechanisms behind lens development possible. Despite the particular emphasis given to the induction of the lens placode, there are still many aspects of the cell biology of lens morphogenesis to be explored. Here, we will revisit the classical detailed description of early lens morphological changes, correlating it with the cell biology mechanisms and with the molecules and signaling pathways identified up to now in chick and mouse embryos. A detailed description of lens development stages helps better understand the timeline of the events involved in early lens morphogenesis. We then point to some key questions that are still open.


Subject(s)
Lens, Crystalline , Animals , Chick Embryo , Lens, Crystalline/embryology , Mice , Morphogenesis
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