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.