Abstract

Maik Christian Bischoff

Title: Plexin/Semaphorin Antagonism Orchestrates Collective Cell Migration and Organ Sculpting by Regulating Epithelial-Mesenchymal Balance

Abstract:Cell behavior emerges from the intracellular distribution of properties like protrusion, contractility, and adhesion. Thus, characteristic emergent rules of collective migration can arise from cell-cell contacts locally tweaking architecture, orchestrating self-regulation during development, wound healing, and cancer progression. The Drosophila testis-nascent-myotube-system allows dissection of contact-dependent migration in vivo at high resolution. Here, we describe a role for the axon guidance factor Plexin A in collective cell migration: maintaining cell-cell interfaces at a precise point on the epithelial-mesenchymal spectrum. This is crucial for testis myotubes to migrate as a continuous sheet, allowing normal sculpting-morphogenesis. Cells must maintain filopodial N-cadherin-based junctions and remain ECM -tethered near cell-cell contacts to spread while collectively moving. Our data further suggest Semaphorin 1b is a Plexin A antagonist, fine-tuning activation. This reveals a contact-dependent mechanism to maintain sheet-integrity during migration, driving organ-morphogenesis. This is relevant for mesenchymal organ-sculpting in other migratory contexts like angiogenesis.

Harry McNamara (Assistant Professor of Molecular, Cellular and Developmental Biology, Yale University)

Title: Decoding and controlling self-organization in stem cell models of embryonic development

Abstract: The arrival of stem cell-based models of embryonic development (organoids, gastruloids, embryo models) presents new opportunities to investigate multicellular self-organization. Although development is often studied as a top-down process in which external spatial cues (such as morphogen gradients) instruct cell fate decisions, it is also thought that internal feedbacks in signaling networks can self-organize pattern formation from the bottom-up. Stem cell models use self-organization to generate cell types and tissue structures which resemble those built by real embryos. Despite rapid advances in stem cell model complexity and detailed comparisons to their in vivo counterparts, we have a comparatively limited understanding of how they emerge from cell signaling interactions. Unlocking the full potential of stem cell models will require not only characterizing their outputs but also understanding how they work.

We investigate stem cell self-organization by programming cells to read and write morphogen signals. By programming cells to record signaling activity, we can link early cell states to future cell fates and decode the origins of pattern formation. By controlling cell signaling with optogenetics, we can re-introduce spatial cues into stem cell models to guide morphogenesis and test predictions of quantitative theories. We will describe recent work applying this approach to study anterior-posterior symmetry breaking in the gastruloid as well as future opportunities in other stem cell developmental models.