Biology subjects

Klemmt, P. A.

Publications and source records attributed to Klemmt, P. A..

3 recordsLinked to original sources

bioRxiv2025

Patterned integrin-laminin adhesion coordinates epithelial collective cell migration

Collective cell migration is essential for development, tissue homeostasis, and disease progression. Although integrin-mediated adhesion is well characterized in single migrating cells in vitro, how integrins coordinate collective epithelial migration in vivo is less clear. Using the zebrafish posterior lateral line primordium (pLLP), we show that integrins 3 and 6 are differentially expressed in the trailing and leading regions of the pLLP, respectively, and that their combined loss induces excessive protrusive activity and slows migration. We further identify laminin 5 (Lama5) as a key basement membrane (BM) component underlying migrating pLLP cells. While loss of laminin 5 alone compromises BM integrity without impairing migration, simultaneous depletion of lama5 and itga6b markedly decreases velocity, and ultimately blocks migration. These findings reveal a robust, redundant adhesion machinery that ensures persistent collective migration in vivo and highlight fundamental principles of epithelial dynamics relevant to development and disease.

developmental biology↗

bioRxiv2025

Vgll4 Proteins limit Organ Size in Zebrafish through Yap1-Dependent and -Independent Mechanisms

Precise control of organ size is crucial during development and homeostasis. Dysregulation of the underlying mechanisms can result in organ malformation and tumorigenesis. Although the Hippo signaling pathway plays a key role in regulating organ growth, the precise regulation of its effectors, YAP1 and WWTR1, remains unclear. To gain insights into tissue growth control during organ formation, we used the zebrafish posterior lateral line primordium (pLLP), a migratory group of epithelial cells that forms sensory organs, as a model. We demonstrate that Yap1 growth-promoting activity in the pLL system is modulated not only in the cytoplasm but also in the nucleus by Vgll4 proteins. We propose a model in which Yap1, together with Tead proteins, ensures that the pLLP contains a sufficient number of cells before migration begins. Vgll4b and Vgll4l, in contrast, function partially redundantly, to limit pLLP cell number, with Vgll4b showing a stronger tumor-suppressor activity. Our data indicate that Vgll4b/4l counteract Yap1 activity by competing with Yap1 for binding to Tead proteins, but also via a Yap1-independent mechanism. Altogether, this study reveals that a precise balance between Yap1 and Vgll4 proteins ensures proper regulation of cell number in the pLLP.

developmental biology↗

bioRxiv2018

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

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.

developmental biology↗