Biology subjects

Narasimha, M.

Publications and source records attributed to Narasimha, M..

4 recordsLinked to original sources

bioRxiv2025

The Dynein-Dynactin complex influences amnioserosa cell morphodynamics and adhesion during Drosophila dorsal closure

The contraction of the amnioserosa, which provides the major force for Drosophila dorsal closure, is powered by apical constriction. While much work has demonstrated the requirement for the spatiotemporal regulation of intracellular forces generated by the actomyosin cytoskeleton in patterning apical constriction, the role of the microtubule cytoskeleton remains poorly understood. We previously uncovered the necessity of apical microtubule meshwork reorganisation in patterning apical constriction dynamics, and demonstrated its reliance on EB1-dependent microtubule growth and Patronin-dependent non-centrosomal nucleation. Here we discover the requirement for Dynein-Dynactin complex functions in patterning cell morphodynamics in the amnioserosa. We show that perturbing this complex in multiple ways, including the use of a mutant that likely disrupts microtubule anchorage rather than transport, alters apical constriction morphodynamics and modulates adherens junction remodelling during amnioserosa cell delamination. The defects we observe are additionally sensitive to ECadherin levels and lead to compromised amnioserosa integrity and adverse dorsal closure outcomes. We suggest that the Dynein-Dynactin complex influences cell morphodynamics in the amnioserosa by enabling the regulation and spatiotemporal coordination of cell adhesion, the mechanistic basis for which remains to be discovered.

cell biology↗

bioRxiv2025

Integrins pattern the Drosophila embryonic neuroepithelium by influencing progenitor morphodynamics, division and position

Gene regulatory networks that confer cell fate and intracellular force generation mechanisms that drive cellular morphodynamics guide the patterning of tissues, but the nature of their interplay is poorly understood. We explore this during Drosophila embryonic neurogenesis whose first step, the delamination of a neuroblast from the surface epithelium, resembles an epithelial to mesenchymal transition (EMT). Using real-time, 3D confocal microscopy combined with quantitative morphometry, we identify robust morphometric state transitions that culminate in the basal delamination of the neuroblast (NB) from an equipotent epidermal proneural cluster, and find that mitotic rounding occurs concomitantly with delamination. We uncover marked heterogeneity and reduced collectivity in the morphodynamics of the NB and its nearest neighbours, and suggest their origins in the morphogenetic activity in the extending germband. We show that the appearance and distribution of the NB and GMC fate determinants Deadpan/dpn and Prospero/pros respectively correlate temporally with distinct morphometric states. We identify changes in cell-cell and cell-substrate adhesion that accompany neuroblast delamination and division and show that the adhesive microenvironment provided by integrin-ECM interactions patterns the neuroepithelium by influencing the spatiotemporal control of cell shape, division and position.

cell biology↗

bioRxiv2022

Actomyosin cables position cell cohorts during Drosophila germband retraction by entraining their morphodynamic and mechanical properties

The unfolding and displacement of the germband during Drosophila germband retraction (GBR) accomplish the straightening of the embryonic anterior-posterior axis. The failure of GBR reduces embryonic viability and results in the mispositioning of the embryonic segments and the gastrointestinal tract. Despite its importance, the cellular, molecular and physical mechanisms that govern the unfolding of the germband and ensure the accurate positioning of cell fields within it remain poorly understood. Here, we uncover the requirement of planar polarized, supracellular, tensile actomyosin cables for entraining cellular morphodynamics, cell field positioning and retraction kinematics. Circumferential, non-constricting cables that form during early retraction ensure the coherence of placode-like cell cohorts, pattern medio-lateral gradients in cell shape and sidedness within it, and dampen retraction speed. Linear, constricting cables that power displacement at the end of retraction enable sequential, multi-tissue, collective T1 transitions to reposition medial cell fields to more posterior locations. Together, our results reveal how the spatiotemporally regulated deployment of actomyosin structures, functioning either as barricades or as purse strings, modulate the speed of tissue unfolding and enable cell field positioning by influencing the morphodynamic and mechanical properties of cell cohorts during morphogenesis.

cell biology↗

bioRxiv2021

Moving patronin foci and growing microtubule plus ends direct the spatiotemporal dynamics of Rho signaling and myosin during apical constriction

The contraction of the amnioserosa by apical constriction provides the major force for Drosophila dorsal closure. The nucleation, movement and dispersal of apicomedial actomyosin complexes generate pulsed constrictions during early dorsal closure whereas persistent apicomedial and circumapical actomyosin complexes drive the unpulsed constrictions that follow. What governs the spatiotemporal assembly of these distinct complexes, endows them with their pulsatile dynamics, and directs their motility remains unresolved. Here we identify an essential role for microtubule growth in regulating the timely contraction of the amnioserosa. We show that a symmetric cage of apical microtubules forms around the coalescing apicomedial myosin complex. An asymmetric tail of microtubules then trails the moving myosin complex and disperses as the myosin complex dissolves. Perturbing microtubule growth reduced the coalescence and movement of apicomedial myosin complexes and redistributed myosin and its activator, Rho kinase to the circumapical pool and altered the cell constriction and tissue contraction dynamics of the amnioserosa. We show that RhoGEF2, the activator of the Rho1 GTPase, is transiently associated with microtubule plus end binding protein EB1 and the apicomedial actomyosin complex. Our results suggest that microtubule growth from moving patronin platforms modulates actomyosin contractility through the spatiotemporal regulation of Rho1 activity. We propose that microtubule reorganisation enables a self-organising, mechanosensitive feedback loop that buffers the tissue against mechanical stresses by modulating actomyosin contractility.

cell biology↗