Lgl resets Par complex membrane loading at mitotic exit to enable asymmetric neural stem cell division.

The Par complex regulates cell polarity in diverse animal cells , but how its localization is restricted to a specific membrane domain remains unclear. We investigated how the tumor suppressor Lethal giant larvae (Lgl) polarizes the Par complex in neural stem cells (NSCs or neuroblasts). In contrast to epithelial cells, where Lgl and the Par complex occupy mutually exclusive membrane domains, Lgl is cytoplasmic when the Par complex is apically polarized in NSCs.

Membrane oscillations driven by Arp2/3 constrict the intercellular bridge during neural stem cell divisions.

After the first furrowing step of animal cell division, the nascent sibling cells remain connected by a thin intercellular bridge (ICB). In isolated cells nascent siblings migrate away from each other to generate tension and constrict the ICB, but less is known about how cells complete cytokinesis when constrained within tissues. We examined the ICBs formed by larval brain neural stem cell (NSC) asymmetric divisions and find that they rely on constriction focused at the central midbody region rather than the flanking arms of isolated cell ICBs.

The cytokinetic midbody mediates asymmetric fate specification at mitotic exit during neural stem cell division.

Asymmetric cell division (ACD) is a broadly used mechanism for generating cellular diversity. Molecules known as fate determinants are segregated during ACD to generate distinct sibling cell fates, but determinants should not be activated until fate can be specified asymmetrically. Determinants could be activated after cell division but many animal cells complete division long after mitosis ends, raising the question of how activation could occur at mitotic exit taking advantage of the unique state plasticity at this time point.

The Drosophila neuroblast polarity cycle at a glance.

Drosophila neural stem cells, or neuroblasts, rapidly proliferate during embryonic and larval development to populate the central nervous system. Neuroblasts divide asymmetrically to create cellular diversity, with each division producing one sibling cell that retains the neuroblast fate and another that differentiates into glia or neurons. This asymmetric outcome is mediated by the transient polarization of numerous factors to the cell cortex during mitosis.

Consumption of a polarized membrane reservoir drives asymmetric membrane expansion during the unequal divisions of neural stem cells.

The asymmetric divisions of Drosophila neural stem cells (NSCs) produce unequally sized siblings, with most volume directed into the sibling that retains the NSC fate. Sibling size asymmetry results from the preferential expansion of the NSC sibling surface during division. Here, we show that a polarized membrane reservoir constructed by the NSC in early mitosis provides the source for expansion.

Actin-dependent membrane polarization reveals the mechanical nature of the neuroblast polarity cycle.

The Par complex directs fate-determinant segregation from the apical membrane of asymmetrically dividing Drosophila neuroblasts. While the physical interactions that recruit the Par complex have been extensively studied, little is known about how the membrane itself behaves during polarization. We examined the membrane dynamics of neuroblasts and surrounding cells using a combination of super-resolution and time-lapse imaging, revealing cellular-scale movements of diverse membrane features during asymmetric division cycles.

A comparison of resveratrol and other polyphenolic compounds on Notch activation and endothelial cell activity.

Resveratrol is a polyphenolic compound produced by plants which makes its way into the human diet through plant-based foods. It has been shown to provide many health benefits, helping to ward of age-related diseases and promoting cardiovascular health. Additionally, resveratrol is a potent activator of the Notch signaling pathway.

Src kinase phosphorylates Notch1 to inhibit MAML binding.

Notch signaling is a form of intercellular communication which plays pivotal roles at various stages in development and disease. Previous findings have hinted that integrins and extracellular matrix may regulate Notch signaling, although a mechanistic basis for this interaction had not been identified. Here, we reveal that the regulation of Notch by integrins and extracellular matrix is carried out by Src family kinases (SFKs) working downstream of integrins.

Beyond the Matrix: The Many Non-ECM Ligands for Integrins.

The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps.

Notch: A multi-functional integrating system of microenvironmental signals.

The Notch signaling cascade is an evolutionarily ancient system that allows cells to interact with their microenvironmental neighbors through direct cell-cell interactions, thereby directing a variety of developmental processes. Recent research is discovering that Notch signaling is also responsive to a broad variety of stimuli beyond cell-cell interactions, including: ECM composition, crosstalk with other signaling systems, shear stress, hypoxia, and hyperglycemia. Given this emerging understanding of Notch responsiveness to microenvironmental conditions, it appears that the classical view of Notch as a mechanism enabling cell-cell interactions, is only a part of a broader function to integrate microenvironmental cues.