Akantsha Jain-Unveiling the choreography of human brain development;Yamini Ravichandran-Topology changes of the regenerating Hydra define actin nematic defects as mechanical organizers of morphogenesis

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• Akantsha Jain,Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland; Yamini Ravichandran,University of Geneva, Switzerland
• Monday 10 February 2025, 14:30-15:30
• Online.

If you have a question about this talk, please contact Jia CHEN.

Akantsha Jain’s talk title: Unveiling the choreography of human brain development-Longterm lightsheet imaging unveils morphodynamics in human brain organoids.

Abstract: Brain organoids enable mechanistic study of human brain development and provide opportunities to explore self-organization in unconstrained developmental systems. We have established long-term light sheet microscopy on unguided multi-mosaic neural organoids (MMOs) generated from fluorescently labeled human induced pluripotent stem cells (iPSCs), which enables tracking of tissue morphology, cell behaviors, and subcellular features over weeks of organoid development. We demultiplex multi-mosaic neural organoids using morphometrics to provide quantitative measurements of tissue and cellular dynamics, using Actin, Tubulin, plasma membrane, nuclei, and Lamin labels, and show that the organoids exhibit tissue state transitions through neural induction, lumenization, and regionalization. We find that despite morphological heterogeneity, different organoids exhibit lumen formation and expansion at a consistent time, coinciding with early neurectoderm switching to late neurectoderm fate. This morphological tissue transition coincides with a switch in underlying gene regulatory networks (GRNs) involving extracellular matrix (ECM) pathway regulators. Presence of a basement membrane rich external ECM promotes cell polarization, cell alignment to form a neuroepithelium, lumen expansion and leads to formation of telencephalic progenitors. However, in absence of external ECM , the tissue transition switch is perturbed forming a heterogenous neuroepithelium with mixed cellular alignment and polarity. This promotes formation of increased neural crest cells and non-telencephalic progenitors. Finally, we show ECM induced patterning guidance is linked to modulations of the WNT and HIPPO signaling pathway, including spatially restricted induction of WLS and YAP1 . Altogether, our work provides a new inroad into studying human brain morphodynamics, and supports a view that mechanosensing dynamics play a central role in constraining brain regionalization.

Yamini Ravichandran’s talk title: Topology changes of the regenerating Hydra define actin nematic defects as mechanical organizers of morphogenesis.

Abstract: Hydra is named after the mythological animal for its regenerative capabilities, but contrary to its mythological counterpart, it only regenerates one head when cut. Here we show that soft compression of head regenerating tissues induces the regeneration of viable, two headed animals. Topological defects in the supracellular nematic organization of actin were previously correlated with the new head regeneration site1. Soft compression creates new topological defects associated with additional heads. To test the necessity of topological defects in head regeneration, we changed the topology of the tissue. By compressing the head regenerating tissues along their body axis, topological defects of the foot and of the regenerating head fused together, forming a toroid with no defects. Perfectly ordered toroids did not regenerate over eight days and eventually disintegrated. Spheroids made from excised body column tissue partially lose their actin order during regeneration. Compression of spheroids generated toroids with actin defects. These tissues regenerated into toroidal animals with functional head and foot, and a bifurcated body. Our results show that topological defects in the actin order are necessary to shape the head of the regenerating Hydra, supporting the notion that actin topological defects are mechanical organizers of morphogenesis.

This talk is part of the Morphogenesis Seminar Series series.

This talk is included in these lists:

• Graduate-Seminars
• Morphogenesis Seminar Series
• Online

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