Hippo signaling is a critical pathway that integrates extrinsic and intrinsic mechanical cues to regulate organ size. Despite its essential role in organogenesis, little is known about its role in cell fate specification and differentiation. Here, we unravel a novel and unexpected role of the Hippo pathway effector Taz (wwtr1) in controlling the size, shape and fate of a unique cell in the zebrafish ovary. We show that wwtr1 mutant females are infertile. In teleosts, fertilization occurs through the micropyle, a funnel-like opening in the chorion, formed by a unique enlarged follicle cell, the micropylar cell (MC). We describe here, for the first time, the mechanism that underlies the differentiation of the MC. Our genetic analyses show that Taz is essential for MC fate acquisition 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. Altogether, we performed the first genetic and molecular characterization of the MC and propose that Taz is a key regulator of MC fate. This article has an associated 'The people behind the papers' interview.

In 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. Abstract word count: 248 words Main text word count: 8639 words Bally-Cuif, L., Schatz, W. J. and Ho, R. K. (1998). Characterization of the zebrafish Orb/CPEB-related RNA binding protein and localization of maternal components in the zebrafish oocyte. Mech Dev 77, 31-47. . Cadherin-catenin complexes during zebrafish oogenesis: heterotypic junctions between oocytes and follicle cells. Biol. Reprod. 61, 692-704. . (2011). Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res 39, e82. Chaigne, A., Campillo, C., Gov, N. S., Voituriez, R., Sykes, C., Verlhac, M. H. and Terret, M. E. (2015). A narrow window of cortical tension guides asymmetric spindle positioning in the mouse oocyte. Nat Commun 6, 6027.Compagnon, J., Barone, V., Rajshekar, S., Kottmeier, R., Pranjic-Ferscha, K., Behrndt, M. and Heisenberg, C.-P. (2014). The notochord breaks bilateral symmetry by controlling cell shapes in the zebrafish laterality organ. Dev Cell 31, 774-783.

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