Commentary

Cell mechanics in early vertebrate development: Yap mechanotransduction controls notochord formation and neural tube patterning

  • Zheng Guo ,
  • Jing Du , *
Expand
  • Key Laboratory of Biomechanics and Mechanobiology (Beihang University), Ministry of Education Beijing Advanced Innovation Center for Biomedical Engineering School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China
* E-mail address: (J. Du).

Received date: 2023-10-26

  Accepted date: 2023-10-29

  Online published: 2023-11-01

Abstract

A recent study published in Science Advances1 showed the influence of Yap on notochord formation and NT (neural tube) patterning in vertebrate embryonic development, and conducted an in-depth study from the perspective of biomechanical signal mechanotransduction. In addition, this study also explored the possible complex interaction between mechanical signals and gene expression. Together, this study provides new insights into the development mechanism of early vertebrate embryos.

Cite this article

Zheng Guo , Jing Du . Cell mechanics in early vertebrate development: Yap mechanotransduction controls notochord formation and neural tube patterning[J]. Mechanobiology in Medicine, 2023 , 1(2) : 100029 -2 . DOI: 10.1016/j.mbm.2023.100029

Yap (Yes-associated protein 1) and Taz (Transcriptional coactivator with PDZ-binding motif) are transcriptional coactivators that play crucial roles in the Hippo signaling pathway, which regulates cell proliferation, tissue homeostasis, and organ size [2]. The mechanism of the yap gene in embryos has been one of the research hotspots in the field of developmental biology. Many studies have revealed the role of yap signaling in vertebrate embryonic development, from preimplantation to organ development. As early as the first cell fate determination in mouse embryos, Yap signaling was activated after polarization of the outer cells, causing the outer cells to differentiate into TE (trophectoderm) [3]. Yap signaling also plays essential roles in organ development. For example, Yap KO (Yap−/−) mice die at E8.5, while Taz KO (Taz−/−) mice develop glomerulocystic kidney disease and pulmonary disease [4,5].
The formation of the notochord and morphogenesis of the vertebrate neural tube are crucial in early vertebrate development. NTDs (neural tube defects) are a common birth defect in humans [6,7]. The complex interplay of genetic and environmental factors in the development of neural tube defects highlights the need for a better understanding of cellular and molecular mechanisms [8]. The complex networks of biochemical signaling have been found to direct notochord and NT development in higher vertebrate embryos, but the precise instructive role of mechanotransduction in cell fate determination and patterning has long remained neglected. During embryonic development, cells constantly receive biophysical stimuli, such as pressure, strain, and fluid flow, and the effects of these biophysical stimuli on embryonic development are often ignored. Mechanotransduction is an important regulatory mechanism that converts mechanical forces into biological signals, revealing environmental features for almost all cells during embryonic development and sensory perception [9,10,11].
Recently, an article entitled “Yap controls notochord formation and neural tube patterning by integrating mechanotransduction with Foxa2 and Shh expression” published in Science Advances revealed the influence of Yap on notochord formation and NT patterning in vertebrate embryonic development, and conducted an in-depth study from the perspective of biomechanical signal mechanotransduction [1]. The authors directly measured the rigidity of the developing NT using atomic force microscopy and found a DV gradient of tissue stiffness before and after NT closure, with the highest rigidity found in the notochord, ventral NT, and FP. These results suggest that there is a DV gradient of tissue rigidity in the early developing NT, suggesting that ventral NT cells may experience higher tension. Their further studies show that DV (Dorsoventral) patterning of the NT and surrounding tissues requires Yap activation, which reads a DV gradient of mechanical forces and promotes the expression of ventralizing factor Shh (Sonic Hedgehog) in the notochord and FP (Floor plate) [12,13,14]. The authors showed that Yap is both necessary and sufficient to control DV patterning by activating FoxA2 (Forkhead box protein) expression in the notochord and synergistically interacting with FoxA2 to activate Shh expression in the FP. This study provides new insights into the development mechanism of early vertebrate embryos. In addition, this study also explored the possible complex interaction between mechanotransduction signals and gene expression, providing a new opportunity for us to understand the molecular mechanism in the development of the nervous system. Our related work in the preprint biorxiv article entitled “Brazil nut effect drives pattern formation in early vertebrate embryos” also gave attention to the regulation of Yap in vertebrate embryogenesis through mechanical signal transduction during the development of mouse blastocysts. Our work mainly focuses on the influence of mechanical factors on cell fate determination during early embryonic development in mice. We found that the spontaneous mechanical oscillation of the blastocyst cavity occurring at the mid-blastocyst stage provides the driving force for EPI (epiblast) and PrE (primitive endoderm) precursor spatial segregation. Moreover, YAP nuclear accumulation in PrE precursors is increased in response to blastocyst cavity oscillation and may play crucial roles in the lineage specification of EPI/PrE cells [15].
In conclusion, this paper provides an interesting and promising research direction, and provides new insights and ideas for the study of early vertebrate embryo development from the perspective of biomechanics. In the future, it will be necessary to further explore and verify the research results to provide new strategies and methods for the treatment and prevention of neural tube defects. Moreover, this interdisciplinary research method also provides us with a new methodology that can better understand the essence of life and develop new therapeutic methods. In addition, whether Yap has the same function and mechanism of action in notochord formation and neural tube patterning in other animals or humans requires further research to improve our understanding.

Ethical approval

This study does not contain any studies with human or animal subjects performed by any of the authors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
[1]
C. Cheng, et al., Yap controls notochord formation and neural tube patterning by integrating mechanotransduction with FoxA2 and Shh expression, Sci. Adv. 9 (2023) eadf6927.

[2]
Y. Zheng, D. Pan, The Hippo signaling pathway in development and disease, Dev. Cell 50 (2019) 264-282.

[3]
J.-L. Maître, et al., Asymmetric division of contractile domains couples cell positioning and fate specification, Nature 536 (2016) 344-348.

[4]
E.M. Morin-Kensicki, B.N. Boone, M. Howell, J.R. Stonebraker, S.L. Milgram, Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic Axis elongation in mice with targeted disruption of Yap65, Mol. Cell Biol. 26 (2006) 77-87.

[5]
R. Makita, Y. Uchijima, K. Nishiyama, T. Amano, H. Kurihara, Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ, Am. J. Physiol. Ren. Physiol. 294 (2008) F542.

[6]
K.S. Au, A. Ashley-Koch, H. Northrup, Epidemiologic and genetic aspects of spina bifida and other neural tube defects, Developmental disabilities research reviews 16 (2010) 6-15.

[7]
J. Diana, H. Muriel, Insights into the etiology of mammalian neural tube closure defects from developmental, genetic and evolutionary studies, J. Dev. Biol. 6 (2018) 22.

[8]
Mitchell L. E. in American Journal of Medical Genetics Part C: Seminars in Medical Genetics. vols. 88-94 (Wiley Online Library).

[9]
S. Piccolo, H.L. Sladitschek-Martens, M. Cordenonsi, Mechanosignaling in vertebrate development, Dev. Biol. 488 (2022) 54-67.

[10]
M. Valet, E.D. Siggia, A.H. Brivanlou, Mechanical regulation of early vertebrate embryogenesis, Nat. Rev. Mol. Cell Biol. 23 (2022).

[11]
Y.-X. Qin, J. Zhao, Mechanobiology in cellular, molecular, and tissue adaptation, Mechanobiology in Medicine (2023) 100022.

[12]
J. Ericson, et al., Sonic hedgehog induces the differentiation of ventral forebrain neurons: a common signal for ventral patterning within the neural tube, Cell 81 (1995) 747-756.

[13]
E. Marti, D.A. Bumcrot, R. Takada, A.P. Mcmahon, Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explan, Nature 375 (1995) 322-325.

[14]
H. Roelink, et al., Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis, Cell 81 (1995) 445-455.

[15]
Z. Guo, J. Yao, X. Zheng, J. Cao, Y. Fan, Brazil Nut Effect Drives Pattern Formation in Early Mammalian Embryos, 2021.

Outlines

/