Mechanosignaling in vertebrate development

Piccolo, Stefano; Sladitschek-Martens, Hanna Lucie; Cordenonsi, Michelangelo

doi:10.1016/j.ydbio.2022.05.005

Cited by 13 publications

(12 citation statements)

References 123 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To explore the induction of TBXT, a target of WNT 48 , we examined YAP signalling as the pathway has been associated with modifying WNT signalling 49,50 and with sensing cell-cell mechanics via LATS1/2 and MST1/2 51 . The role of YAP signalling during trunk formation remains unclear despite YAP null mice exhibiting a truncated axis 52 and YAP being implicated in controlling the segmentation clock 53 .…”

Section: Resultsmentioning

confidence: 99%

Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation

Rito

Libby

Demuth

et al. 2023

Preprint

View full text Add to dashboard Cite

The formation of the vertebrate body involves the coordinated and progressive production of trunk tissues from progenitors located in the posterior of the embryo. In vitro models based on pluripotent stem cells (PSCs) replicate aspects of this process, but they lack some tissue components normally present in the trunk. Most strikingly, the notochord, a hallmark of chordates and the source of midline signals that pattern surrounding tissues, is absent from current models of human trunk formation. To investigate how trunk tissue is formed, we performed single-cell transcriptomic analysis of chick embryos. This delineated molecularly discrete progenitor populations, which we spatially locate in the embryo, compare across species, and relate to signalling activity. Guided by this map, we determined how differentiating human PSCs develop a stereotypical spatial organization of tissue types. We found that LATS1/2 repression of YAP activity, in conjunction with FGF-mediated MAPK activation, induced the transcription factor Bra/TBXT and facilitated WNT signaling. In addition, inhibiting a WNT-induced NODAL and BMP signaling cascade at the appropriate time regulated the proportions of different tissue types produced, including notochordal cells. We used this information to create an integrated 3D model of human gastrulation undergoing morphogenetic movements to produce elongated structures with a notochord and spatially patterned neural tissue formation. Together the data provide insight into the mechanisms responsible for the formation of the tissues that comprise the vertebrate trunk and pave the way for future studies of patterning in a tissue-like environment.

show abstract

Section: Resultsmentioning

confidence: 99%

Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation

Rito

Libby

Demuth

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Interestingly, PS markers such as T-Bra and Mixl1 are not strongly impacted, suggesting that changes in adhesion and motility do not alter PS identity in Pgr-KO cells. When PS cells are specified into mesoderm progenitors, changes in ECM–cell and cell–cell interactions are essential to generate the physical environment and chemical gradient driving signaling response [ 45 ]. RNAseq analysis shows that ECM proteins such as Laminins and Collagens are upregulated in extraembryonic and cardiac mesoderm ( Figure 6 B), while integrin expression indicates a cell-type-specific pattern, with Itga3 and Itga4 differently expressed in extraembryonic mesoderm and cardiac mesoderm, respectively.…”

Section: Resultsmentioning

confidence: 99%

Progesterone Receptor Modulates Extraembryonic Mesoderm and Cardiac Progenitor Specification during Mouse Gastrulation

Drozd

Mariani

Guo

et al. 2022

IJMS

View full text Add to dashboard Cite

Progesterone treatment is commonly employed to promote and support pregnancy. While maternal tissues are the main progesterone targets in humans and mice, its receptor (PGR) is expressed in the murine embryo, questioning its function during embryonic development. Progesterone has been previously associated with murine blastocyst development. Whether it contributes to lineage specification is largely unknown. Gastrulation initiates lineage specification and generation of the progenitors contributing to all organs. Cells passing through the primitive streak (PS) will give rise to the mesoderm and endoderm. Cells emerging posteriorly will form the extraembryonic mesodermal tissues supporting embryonic growth. Cells arising anteriorly will contribute to the embryonic heart in two sets of distinct progenitors, first (FHF) and second heart field (SHF). We found that PGR is expressed in a posterior–anterior gradient in the PS of gastrulating embryos. We established in vitro differentiation systems inducing posterior (extraembryonic) and anterior (cardiac) mesoderm to unravel PGR function. We discovered that PGR specifically modulates extraembryonic and cardiac mesoderm. Overexpression experiments revealed that PGR safeguards cardiac differentiation, blocking premature SHF progenitor specification and sustaining the FHF progenitor pool. This role of PGR in heart development indicates that progesterone administration should be closely monitored in potential early-pregnancy patients undergoing infertility treatment.

show abstract

“…252 A detailed review of the role of mechanotransduction in embryonic development and cell fate determination has been discussed in these references. 253,254 During the process of gastrulation, the embryo differentiates into three germ layers: ectoderm, mesoderm, and endoderm. Cellular movement and rearrangement place the three germ layers in their respective positions, which leads to the establishment of the body plan and differentiation of complex organs.…”

Section: Mechanical Regulation Of Gene Expression In Cell Fate Determ...mentioning

confidence: 99%

Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation

Mishra,

Chakraborty,

Niharika

et al. 2024

J of Cellular Biochemistry

View full text Add to dashboard Cite

Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in the cell's physical surroundings. These changes of forces impose a mechanical tension within the intracellular protein network (both cytosolic and nuclear). Mechanical tension could be released by a series of protein–protein interactions often facilitated by membrane lipids, lectins and sugar molecules and thus generate a type of signal to drive cellular processes, including cell differentiation, polarity, growth, adhesion, movement, and survival. Recent experimental data have accentuated the molecular mechanism of this mechanical signal transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins in the cell's plasma membrane discern the physical forces and channel the information to the cell interior. Cells respond to the message by altering their cytoskeletal arrangement and directly transmitting the signal to the nucleus through the connection of the cytoskeleton and nucleoskeleton before the information despatched to the nucleus by biochemical signaling pathways. Nuclear transmission of the force leads to the activation of chromatin modifiers and modulation of the epigenetic landscape, inducing chromatin reorganization and gene expression regulation; by the time chemical messengers (transcription factors) arrive into the nucleus. While significant research has been done on the role of mechanotransduction in tumor development and cancer progression/metastasis, the mechanistic basis of force‐activated carcinogenesis is still enigmatic. Here, in this review, we have discussed the various cues and molecular connections to better comprehend the cellular mechanotransduction pathway, and we also explored the detailed role of some of the multiple players (proteins and macromolecular complexes) involved in mechanotransduction. Thus, we have described an avenue: how mechanical stress directs the epigenetic modifiers to modulate the epigenome of the cells and how aberrant stress leads to the cancer phenotype.

show abstract

Mechanosignaling in vertebrate development

Cited by 13 publications

References 123 publications

Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation

Notochord and axial progenitor generation by timely BMP and NODAL inhibition during vertebrate trunk formation

Progesterone Receptor Modulates Extraembryonic Mesoderm and Cardiac Progenitor Specification during Mouse Gastrulation

Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation

Contact Info

Product

Resources

About