Summary The notochord, a conserved axial structure required for embryonic axis elongation and spine development, consists of giant vacuolated cells surrounded by an epithelial sheath [1–3]. During morphogenesis, vacuolated cells maintain their structural integrity despite being under constant mechanical stress [4]. We hypothesized that the high density of caveolae present in vacuolated cells [5, 6] could buffer mechanical tension. Caveolae are 50–80 nm membrane invaginations lined by cage-like polygonal structures [7, 8] formed by caveolin 1 (Cav1) or Cav3, and one of the cavin proteins [6, 9–11]. Recent in vitro work has shown that plasma membrane caveolae constitute a membrane reservoir that can buffer mechanical stresses such as stretching or osmotic swelling [12]. Moreover, mechanical integrity of vascular and muscle cells is partly dependent on caveolae [13–15]. However, the in vivo mechano-protective roles of caveolae have only begun to be explored. Using zebrafish mutants for cav1, cav3 and cavin1b, we show that caveolae are essential for notochord integrity. Upon loss of caveolae function, vacuolated cells collapse at discrete positions under the mechanical strain of locomotion. Then, sheath cells invade the inner notochord and differentiate into vacuolated cells, thereby restoring notochord function and allowing normal spine development. Our data further indicate that nucleotides released by dying vacuolated cells promote sheath cell vacuolization and trans-differentiation. This work reveals a novel structural role for caveolae in vertebrates and provides unique insights into the mechanisms that safeguard notochord and spine development.

Cell migration is essential for morphogenesis, for organ formation and homeostasis, with relevance for clinical conditions. The migration of primordial germ cells (PGCs) is a useful model to study this process in the context of the developing embryo. Zebrafish PGC migration depends on the formation of cellular protrusions in form of blebs, a type of protrusion found in various cell types. Here we report on the mechanisms allowing the inflation of the membrane during bleb formation. We show that the rapid expansion of the protrusion depends on membrane invaginations that are localized preferentially at the cell front. The formation of these invaginations requires the function of Cdc42, and their unfolding allows bleb inflation and dynamic cell-shape changes performed by migrating cells. Inhibiting the formation and release of the invaginations strongly interfered with bleb formation, cell motility and with the ability of the cells to reach their target.

Lubkin SR, Bagnat M. 2018 Tissue selforganization underlies morphogenesis of the notochord. Phil. Trans. R. Soc. B 373: 20170320. http://dx.The notochord is a conserved axial structure that in vertebrates serves as a hydrostatic scaffold for embryonic axis elongation and, later on, for proper spine assembly. It consists of a core of large fluid-filled vacuolated cells surrounded by an epithelial sheath that is encased in extracellular matrix. During morphogenesis, the vacuolated cells inflate their vacuole and arrange in a stereotypical staircase pattern. We investigated the origin of this pattern and found that it can be achieved purely by simple physical principles. We are able to model the arrangement of vacuolated cells within the zebrafish notochord using a physical model composed of silicone tubes and water-absorbing polymer beads. The biological structure and the physical model can be accurately described by the theory developed for the packing of spheres and foams in cylinders. Our experiments with physical models and numerical simulations generated several predictions on key features of notochord organization that we documented and tested experimentally in zebrafish. Altogether, our data reveal that the organization of the vertebrate notochord is governed by the density of the osmotically swelling vacuolated cells and the aspect ratio of the notochord rod. We therefore conclude that self-organization underlies morphogenesis of the vertebrate notochord.This article is part of the Theo Murphy meeting issue on 'Mechanics of development'.

Background Although surveillance systems used to mitigate disasters serve essential public health functions, communities of color have experienced disproportionate harms (eg, criminalization) as a result of historic and enhanced surveillance. Methods To address this, we developed and piloted a novel, equity-based scoring system to evaluate surveillance systems regarding their potential and actual risk of adverse effects on communities made vulnerable through increased exposure to policing, detention/incarceration, deportation, and disruption of access to social services or public resources. To develop the scoring system, we reviewed the literature and surveyed an expert panel on surveillance to identify specific harms (eg, increased policing) that occur through surveillance approaches. Results Scores were based on type of information collected (individual and/or neighborhood level) and evidence of sharing information with law enforcement. Scores were 0 (no risk of harm identified), 1 (potential for risk), 2 (evidence of risk), and U (data not publicly accessible). To pilot the scoring system, 44 surveillance systems were identified between June 2020 and October 2020 through an environmental scan of systems directly related to COVID-19 (n=21), behavioral and health-related services (n=11), and racism and racism-related factors (n=12). A score of 0-2 was assigned to 91% (n=40) of the systems; 9% were scored U; 30% (n=13) scored a 0. Half scored a 1 (n=22), indicating a “potential for the types of harm of concern in this analysis.” “Evidence of harm,” a score of 2, was found for 12% (n=5). Conclusions The potential for surveillance systems to compromise the health and well-being of racialized and/or vulnerable populations has been understudied. This project developed and piloted a scoring system to accomplish this equity-based imperative. The nobler pursuits of public health to improve the health for all must be reconciled with these potential harms.