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Lehtimaki, J. I.

Publications and source records attributed to Lehtimaki, J. I..

2 recordsLinked to original sources

Spatiotemporal Coordination of Guidance Cues Directs Multipolar Migration During Retinal Lamination

Multipolar migration is a conserved neuronal migration mode in the developing brain, enabling emerging neurons to navigate crowded environments and reach precise laminar positions. Yet how these cells interpret external cues to guide their migration remains unclear. We investigate this question in the developing vertebrate retina using horizontal cells as a model. Combining transcriptomics, targeted CRISPR screening, and live imaging, we reveal the spatiotemporal guidance system underlying horizontal cell lamination: repulsive Slit1b/2-Robo2 signaling in the amacrine cell layer is essential to initiate apical horizontal cell migration, while attractive Neurturin-Gfr1 signaling from photoreceptors fine-tunes final positioning beneath the photoreceptor layer. Disruption of these pathways causes basal retention of horizontal cells, highlighting the importance of spatially coordinated signaling for proper lamination and functional retinal circuitry. Our results uncover how positional signals and tissue architecture cooperate to achieve neuronal precision, an organizing principle likely relevant across the developing central nervous system.

developmental biology↗

Generation of stress fibers through myosin-driven re-organization of the actin cortex

Contractile actomyosin bundles, stress fibers, govern key cellular processes including migration, adhesion, and mechanosensing. Stress fibers are thus critical for developmental morphogenesis. The most prominent actomyosin bundles, ventral stress fibers, are generated through coalescence of pre-existing stress fiber precursors. However, whether stress fibers can assemble through other mechanisms has remained elusive. We report that stress fibers can also form without requirement of pre-existing actomyosin bundles. These structures, which we named cortical stress fibers, are embedded in the cell cortex and assemble preferentially underneath the nucleus. In this process, non-muscle myosin II pulses orchestrate the reorganization of cortical actin meshwork into regular bundles, which promote reinforcement of nascent focal adhesions, and subsequent stabilization of the cortical stress fibers. These results identify a new mechanism by which stress fibers can be generated de novo from the actin cortex, and establish role for stochastic myosin pulses in the assembly of functional actomyosin bundles.

cell biology↗