Embryonic development is a coordination of multicellular biochemical patterning and morphogenetic movements. Last decades revealed the close control of myosin-II-dependent biomechanical morphogenesis by patterning gene expression, with constant progress in the understanding of the underlying molecular mechanisms. Reversed control of developmental gene expression and of myosin-II patterning by the mechanical strains developed by morphogenetic movements was recently revealed at Drosophila gastrulation, through mechanotransduction processes involving the Armadillo/beta-catenin and the downstream of Fog Rho pathways. Here, we present the theoretical (simulations integrating the accumulated knowledge in the genetics of early embryonic development and morphogenesis) and the experimental (genetic and biophysical control of morphogenetic movements) tools having allowed the uncoupling of pure genetic inputs from pure mechanical inputs in the regulation of gene expression and myosin-II patterning. Specifically, we describe the innovative magnetic tweezers tools we have set up to measure and apply physiological strains and forces in vivo, from the inside of the tissue, to modulate and mimic morphogenetic movements in living embryos. We discuss mechanical induction incidence in tumor development and perspective in evolution.
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http://dx.doi.org/10.1016/S0091-679X(10)98012-6 | DOI Listing |
Nat Cell Biol
January 2025
Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.
Gastrulation marks a pivotal stage in mammalian embryonic development, establishing the three germ layers and body axis through lineage diversification and morphogenetic movements. However, studying human gastrulating embryos is challenging due to limited access to early tissues. Here we show the use of spatial transcriptomics to analyse a fully intact Carnegie stage 7 human embryo at single-cell resolution, along with immunofluorescence validations in a second embryo.
View Article and Find Full Text PDFCommun Biol
January 2025
Freie Universität Berlin, Institute for Chemistry and Biochemistry, Thielallee 63, 14195, Berlin, Germany.
Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs).
View Article and Find Full Text PDFCase Rep Genet
December 2024
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan.
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder caused by heterozygous pathogenic variants and is characterized by both progressive heterotopic ossification of the soft tissues and congenital malformations of the great toe. In addition to pathological skeletal metamorphosis, patients with FOP experience diverse neurological symptoms such as chronic pain and involuntary movements; however, little is known about the association between FOP and epileptic seizures. We report the case of a young boy with FOP who sustained multiple major fractures due to epileptic loss of consciousness.
View Article and Find Full Text PDFElife
December 2024
Sorbonne Université, Centre National de la Recherche Scientifique (CNRS UMR7622), Institut de Biologie Paris-Seine (IBPS), Developmental Biology Laboratory, Paris, France.
Despite recent progress, the complex roles played by the extracellular matrix in development and disease are still far from being fully understood. Here, we took advantage of the zebrafish mutation which affects Laminin γ1, a major component of basement membranes, to explore its role in the development of the olfactory system. Following a detailed characterisation of Laminin distribution in the developing olfactory circuit, we analysed basement membrane integrity, olfactory placode and brain morphogenesis, and olfactory axon development in mutants, using a combination of immunochemistry, electron microscopy and quantitative live imaging of cell movements and axon behaviours.
View Article and Find Full Text PDFThe formation of the vertebrate body involves the coordinated production of trunk tissues from progenitors located in the posterior of the embryo. Although in vitro models using pluripotent stem cells replicate aspects of this process, they lack crucial components, most notably the notochord-a defining feature of chordates that patterns surrounding tissues. Consequently, cell types dependent on notochord signals are absent from current models of human trunk formation.
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