Skip to main page content
U.S. flag
See More

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Oct;96(11):1229-1237.
doi: 10.1177/0022034517719886. Epub 2017 Jul 12.

Hippo Pathway: An Emerging Regulator of Craniofacial and Dental Development

J Wang  1 , J F Martin  1   2
Affiliations
Review

Hippo Pathway: An Emerging Regulator of Craniofacial and Dental Development

J Wang et al. J Dent Res. 2017 Oct.

Abstract

The evolutionarily conserved Hippo signaling pathway is a vital regulator of organ size that fine-tunes cell proliferation, apoptosis, and differentiation. A number of important studies have revealed critical roles of Hippo signaling and its effectors Yap (Yes-associated protein) and Taz (transcriptional coactivator with PDZ binding motif) in tissue development, homeostasis, and regeneration, as well as in tumorigenesis. In addition, recent studies have shown evidence of crosstalk between the Hippo pathway and other key signaling pathways, such as Wnt signaling, that not only regulates developmental processes but also contributes to disease pathogenesis. In this review, we summarize the major discoveries in the field of Hippo signaling and what has been learned about its regulation and crosstalk with other signaling pathways, with a particular focus on recent findings involving the Hippo-Yap pathway in craniofacial and tooth development. New and exciting studies of the Hippo pathway are anticipated that will significantly improve our understanding of the molecular mechanisms of human craniofacial and tooth development and disease and will ultimately lead to the development of new therapies.

Keywords: Taz; Yap; cranial neural crest; molecular signaling; orofacial morphogenesis; tooth.

PubMed Disclaimer

Conflict of interest statement

The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
A brief summary of the intracellular Hippo pathway in mammals. The core Hippo pathway in mammals is composed of evolutionarily conserved kinases, including the Mst1/2 (Hpo in Drosophila), Sav1 (Sav in Drosophila), and Lats1/2 (Wts in Drosophila) kinases. When Hippo signaling is active, this kinase cascade is sequentially phosphorylated as shown, eventually resulting in the phosphorylation of Yap and Taz to promote their interaction with 14-3-3 protein and their degradation in the cytoplasm. Without repression by Hippo signaling, Yap and Taz can shuttle into the nucleus and bind to transcription factors (e.g., Tead) to regulate the transcription of target genes involved in different physiologic processes, such as cell proliferation, differentiation, and migration.
Figure 2.
Figure 2.
A model for the regulation and signaling crosstalk of the Hippo pathway. As shown in the art, the Hippo pathway is regulated by mechanical signals, microRNAs, and crosstalk with Wnt, bone morphogenic protein, and TGF-β pathways. In addition, many other signals, such as G protein–coupled receptor and Notch pathway signals, can regulate or crosstalk with the Hippo pathway. ECM, extracellular matrix.
See this image and copyright information in PMC

References

    1. Abe Y, Ohsugi M, Haraguchi K, Fujimoto J, Yamamoto T. 2006. Lats2-ajuba complex regulates gamma-tubulin recruitment to centrosomes and spindle organization during mitosis. FEBS Lett. 580(3):782–788. - PubMed
    1. Alarcón C, Zaromytidou AI, Xi Q, Gao S, Yu J, Fujisawa S, Barlas A, Miller AN, Manova-Todorova K, Macias MJ, et al. 2009. Nuclear CDKs drive Smad transcriptional activation and turnover in BMP and TGF-beta pathways. Cell. 139(4):757–769. - PMC - PubMed
    1. Aragona M, Panciera T, Manfrin A, Giulitti S, Michielin F, Elvassore N, Dupont S, Piccolo S. 2013. A mechanical checkpoint controls multicellular growth through Yap/Taz regulation by actin-processing factors. Cell. 154(5):1047–1059. - PubMed
    1. Azzolin L, Panciera T, Soligo S, Enzo E, Bicciato S, Dupont S, Bresolin S, Frasson C, Basso G, Guzzardo V, et al. 2014. Yap/Taz incorporation in the β-catenin destruction complex orchestrates the Wnt response. Cell. 158(1):157–170. - PubMed
    1. Azzolin L, Zanconato F, Bresolin S, Forcato M, Basso G, Bicciato S, Cordenonsi M, Piccolo S. 2012. Role of Taz as mediator of Wnt signaling. Cell. 151(7):1443–1456. - PubMed

LinkOut - more resources