Biology subjects

Falco, C.

Publications and source records attributed to Falco, C..

3 recordsLinked to original sources

bioRxiv2025

Epigenetic control of microglial developmental milestones from proliferative progenitors to efficient phagocytes

Early immune perturbations increase the risk of neurodegenerative and neurodevelopmental disorders, yet the mechanisms underlying the maturation of microglia, the resident immune cells of the brain parenchyma, remain poorly defined. Specifically, how proliferation, morphological differentiation, and phagocytosis are coordinated among microglia progenitors as they colonize the embryonic brain remains unclear. Here, we combined mathematical modeling with spatiotemporal analyses of the murine hippocampus and cerebellum from postnatal day 2 (P2) to P60 to reconstruct the trajectory of microglial development. We identified a proliferative-to-quiescent (P/Q) switch around P3/P4 that preceded the acquisition of morphological complexity and efficient phagocytosis and was accompanied by coordinated shifts in cell-cycle dynamics and metabolic state. Strikingly, this P/Q switch was recapitulated in repopulation contexts in mice and in the human fetal brain, where later stages displayed enhanced phagocytic function coupled to reduced proliferation. Perturbing the proliferative phase through pharmacological or genetic disruption of CSF1R signaling impaired subsequent microglial complexity and phagocytosis efficiency, revealing an unexpected reliance of phagocytosis on proliferation-driven colonization. Finally, we show that microglia stepwise maturation during development is associated with chromatin remodeling and driven by the epigenetic regulator Ikaros. Together, these findings uncover the sequential milestones of microglial development, revealing a potential period of early vulnerability and establishing an unexpected linkage between proliferation and phagocytosis essential to understanding how these processes are coordinated in neurodegenerative disorders.

neuroscience↗

bioRxiv2025

Collective Transitions from Orbiting to Matrix Invasion in 3D Multicellular Spheroids

Coordinated cell rotation along a curved matrix interface can sculpt epithelial tissues into spherical morphologies. Subsequently, radially-oriented invasion of multicellular strands or branches can occur by local remodeling of the confining matrix. These symmetry-breaking transitions emerge from the dynamic reciprocity between cells and matrix, but remain poorly understood. Here, we show that epithelial cell spheroids collectively transition from circumferential orbiting to radial invasion via bi-directional interactions with the surrounding matrix curvature. Initially, spheroids exhibit an ellipsoidal shape but become rounded as orbiting occurs. However, cells gradually reorient from coordinated rotation towards outward strand invasion due to the accumulation of contractile tractions at discrete sites. Remarkably, the initial ellipsoid morphology predicts subsequent invasion of 2-4 strands roughly aligned with the major axis. We then perturb collective migration using osmotic pressure, showing that orbiting can be arrested and invasion can be reversed. We also investigate coordinated orbiting in "mosaic" spheroids, showing a small fraction of "leader" cells with weakened cell-cell adhesions can impede collective orbiting but still invade into the matrix. Finally, we establish a minimal self-propelled particle model to elucidate how collective orbiting is mediated by the crosstalk of cell-cell and cell-matrix adhesion along a curved boundary. Altogether, this work elucidates how tissue morphogenesis is governed by the interplay of collective behaviors and the local curvature of the cell-matrix, with relevance for embryonic development and tumor progression.

biophysics↗

bioRxiv2020

Are isokinetic leg torques and kick velocity reliable predictors for competitive success in taekwondo athletes?

The aim of the study was to analyzed the relationship between isokinetic knee and hip peak torques and Roundhouse-kick velocities and expertise level (Elite vs. Subelite) of Taekwondo athletes. Seven elite and seven sub-elite athletes were tested for kick kinematic, power of impact and for isokinetic peak torque (PT) at slow (60°/s) and high (240°/s) concentric mode. PTs were compared between groups and correlated with the data of kick performance. It was found inter-group differences in hip flexors and extensors PT at the isokinetic fast speed. The hip flexion PT at 60°/s and 240°/s were negatively correlated with the kick time (R = −0.46, and R = −0.62, respectively). Hip flexion torque at 60°/s was also positively correlated (R = 0.52) with the peak of linear velocity of the foot (LVF) and the power of impact (R = 0.51). Peak torque of hip extension at 60°/s and hip abduction at 240°/s were correlated with the LVF (R= 0.56 and R = 0.46). Discriminant analysis presented an accuracy of 85.7% in predicting expertise level based on fast torques of hip flexion and extension and on the knee extension velocity during the kick. This study demonstrated that hip muscles strength is probably the dominant muscular factor for determining kick performance. Knee angular velocity combined with hip torques are the best discriminators for the competitive level in taekwondo athletes.View Full Text

physiology↗