The Hippo pathway effector Taz is required for cell fate specification and fertilization in zebrafish

SUMMARYIn the last decade, Hippo signaling has emerged as a critical pathway integrating extrinsic and intrinsic mechanical cues to regulate cell proliferation and survival, tissue morphology and organ size in vivo. Despite its essential role in organogenesis, surprisingly much less is known about how it connects biomechanical signals to control of cell fate and cell size during development. Here we unravel a novel and unexpected role of the Hippo pathway effector Taz (wwtr1) in the control of cell size and cell fate specification. In teleosts, fertilization occurs through a specific structure at the animal pole, called the micropyle. This opening in the chorion is formed during oogenesis by a specialized somatic follicle cell, the micropylar cell (MC). The MC has a peculiar shape and is much larger than its neighboring follicle cells but the mechanisms underlying its specification and cell shape acquisition are not known. Here we show that Taz is essential for the specification of the MC and subsequent micropyle formation in zebrafish. We identify Taz as the first bona fide MC marker and show that Taz is specifically and strongly enriched in the MC precursor before the cell can be identified morphologically. Altogether, our genetic data and molecular characterization of the MC lead us to propose that Taz is a key regulator of the MC fate activated by physical cues emanating from the oocyte to initiate the MC morphogenetic program. We describe here for the first time the mechanism underlying the specification of the MC fate.

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Nuclear beta-catenin is required to specify vegetal cell fates in the sea urchin embryo

Development ◽

10.1242/dev.126.2.345 ◽

1999 ◽

Vol 126 (2) ◽

pp. 345-357 ◽

Cited By ~ 31

Author(s):

C.Y. Logan ◽

J.R. Miller ◽

M.J. Ferkowicz ◽

D.R. McClay

Keyword(s):

Cell Fate ◽

Sea Urchin ◽

Beta Catenin ◽

Cell Fate Specification ◽

Cell Fates ◽

Cell Stage ◽

Animal Pole ◽

Fate Specification ◽

The Relationship ◽

Vegetal Cell

Beta-catenin is thought to mediate cell fate specification events by localizing to the nucleus where it modulates gene expression. To ask whether beta-catenin is involved in cell fate specification during sea urchin embryogenesis, we analyzed the distribution of nuclear beta-catenin in both normal and experimentally manipulated embryos. In unperturbed embryos, beta-catenin accumulates in nuclei that include the precursors of the endoderm and mesoderm, suggesting that it plays a role in vegetal specification. Using pharmacological, embryological and molecular approaches, we determined the function of beta-catenin in vegetal development by examining the relationship between the pattern of nuclear beta-catenin and the formation of endodermal and mesodermal tissues. Treatment of embryos with LiCl, a known vegetalizing agent, caused both an enhancement in the levels of nuclear beta-catenin and an expansion in the pattern of nuclear beta-catenin that coincided with an increase in endoderm and mesoderm. Conversely, overexpression of a sea urchin cadherin blocked the accumulation of nuclear beta-catenin and consequently inhibited the formation of endodermal and mesodermal tissues including micromere-derived skeletogenic mesenchyme. In addition, nuclear beta-catenin-deficient micromeres failed to induce a secondary axis when transplanted to the animal pole of uninjected host embryos, indicating that nuclear beta-catenin also plays a role in the production of micromere-derived signals. To examine further the relationship between nuclear beta-catenin in vegetal nuclei and micromere signaling, we performed both transplantations and deletions of micromeres at the 16-cell stage and demonstrated that the accumulation of beta-catenin in vegetal nuclei does not require micromere-derived cues. Moreover, we demonstrate that cell autonomous signals appear to regulate the pattern of nuclear beta-catenin since dissociated blastomeres possessed nuclear beta-catenin in approximately the same proportion as that seen in intact embryos. Together, these data show that the accumulation of beta-catenin in nuclei of vegetal cells is regulated cell autonomously and that this localization is required for the establishment of all vegetal cell fates and the production of micromere-derived signals.

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Single cell transplantation reveals interspecific cell communication in Drosophila chimeras

Development ◽

10.1242/dev.109.4.821 ◽

1990 ◽

Vol 109 (4) ◽

pp. 821-832 ◽

Cited By ~ 2

Author(s):

T. Becker ◽

G.M. Technau

Keyword(s):

Cell Cycle ◽

Single Cell ◽

Cell Size ◽

Cell Fate ◽

Cell Communication ◽

Host Tissue ◽

Cell Fate Specification ◽

Fate Specification ◽

Common Strategy ◽

Invertebrate Development

Cell-cell communication is not only a common strategy for cell fate specification in vertebrates, but plays important roles in invertebrate development as well. We report here on experiments testing the compatibility of mechanisms specifying cell fate among six different Drosophila species. Following interspecific transplantation, the development of single ectodermal cells was traced in order to test their abilities to proliferate and differentiate in a heterologous environment. Despite considerable differences in cell size and length of cell cycle among some of the species, the transplants gave rise to fully differentiated clones that were integrated into the host tissue. Clones comprised cells of epidermal and/or neural histotypes, indicating that mechanisms mediating the epidermal/neural dichotomy in the ectoderm are conserved between the species. Cells of the neural lineages differentiated into neurones, glia, or both. Moreover, heterologous neurones sent out axons that followed major pathways along nerves and within the neuropile, demonstrating their ability to recognize positional cues in the heterologous CNS of the host.

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Faculty Opinions recommendation of The expression and function of the achaete-scute genes in Tribolium castaneum reveals conservation and variation in neural pattern formation and cell fate specification.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016251.200311 ◽

2003 ◽

Author(s):

Patricia Simpson

Keyword(s):

Pattern Formation ◽

Cell Fate ◽

Tribolium Castaneum ◽

Cell Fate Specification ◽

Fate Specification ◽

And Function

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Faculty Opinions recommendation of The WEREWOLF MYB protein directly regulates CAPRICE transcription during cell fate specification in the Arabidopsis root epidermis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1028584.342203 ◽

2005 ◽

Author(s):

Liam Dolan

Keyword(s):

Cell Fate ◽

Cell Fate Specification ◽

Arabidopsis Root ◽

Fate Specification ◽

Root Epidermis ◽

Myb Protein

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Faculty Opinions recommendation of Subcellular localization and functional domain studies of DEFECTIVE KERNEL1 in maize and Arabidopsis suggest a model for aleurone cell fate specification involving CRINKLY4 and SUPERNUMERARY ALEURONE LAYER1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.720401353.793504094 ◽

2015 ◽

Author(s):

David Jackson

Keyword(s):

Subcellular Localization ◽

Cell Fate ◽

Functional Domain ◽

Cell Fate Specification ◽

Aleurone Cell ◽

Fate Specification

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YAP and endothelin-1 signaling: an emerging alliance in cancer

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01827-8 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Piera Tocci ◽

Giovanni Blandino ◽

Anna Bagnato

Keyword(s):

Signaling Pathways ◽

Cell Fate ◽

Therapeutic Option ◽

Hippo Pathway ◽

Signaling Network ◽

Nuclear Accumulation ◽

Binding Motif ◽

Mutant P53 ◽

Endothelin 1 ◽

The Hippo Pathway

AbstractThe rational making the G protein-coupled receptors (GPCR) the centerpiece of targeted therapies is fueled by the awareness that GPCR-initiated signaling acts as pivotal driver of the early stages of progression in a broad landscape of human malignancies. The endothelin-1 (ET-1) receptors (ET-1R), known as ETA receptor (ETAR) and ETB receptor (ETBR) that belong to the GPCR superfamily, affect both cancer initiation and progression in a variety of cancer types. By the cross-talking with multiple signaling pathways mainly through the scaffold protein β-arrestin1 (β-arr1), ET-1R axis cooperates with an array of molecular determinants, including transcription factors and co-factors, strongly affecting tumor cell fate and behavior. In this scenario, recent findings shed light on the interplay between ET-1 and the Hippo pathway. In ETAR highly expressing tumors ET-1 axis induces the de-phosphorylation and nuclear accumulation of the Hippo pathway downstream effectors, the paralogous transcriptional cofactors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). Recent evidence have discovered that ET-1R/β-arr1 axis instigates a transcriptional interplay involving YAP and mutant p53 proteins, which share a common gene signature and cooperate in a oncogenic signaling network. Mechanistically, YAP and mutp53 are enrolled in nuclear complexes that turn on a highly selective YAP/mutp53-dependent transcriptional response. Notably, ET-1R blockade by the FDA approved dual ET-1 receptor antagonist macitentan interferes with ET-1R/YAP/mutp53 signaling interplay, through the simultaneous suppression of YAP and mutp53 functions, hampering metastasis and therapy resistance. Based on these evidences, we aim to review the recent findings linking the GPCR signaling, as for ET-1R, to YAP/TAZ signaling, underlining the clinical relevance of the blockade of such signaling network in the tumor and microenvironmental contexts. In particular, we debate the clinical implications regarding the use of dual ET-1R antagonists to blunt gain of function activity of mutant p53 proteins and thereby considering them as a potential therapeutic option for mutant p53 cancers. The identification of ET-1R/β-arr1-intertwined and bi-directional signaling pathways as targetable vulnerabilities, may open new therapeutic approaches able to disable the ET-1R-orchestrated YAP/mutp53 signaling network in both tumor and stromal cells and concurrently sensitizes to high-efficacy combined therapeutics.

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