Epithelial folding is typically driven by localized actomyosin contractility. However, it remains unclear how epithelia deform when myosin levels are low and uniform. In the Drosophila gastrula, dorsal fold formation occurs despite a lack of localized myosin changes, while the fold-initiating cells reduce cell height following basal shifts of polarity via an unknown mechanism. We show that cell shortening depends on an apical microtubule network organized by the CAMSAP protein Patronin. Prior to gastrulation, microtubule forces generated by the minus-end motor dynein scaffold the apical cell cortex into a dome-like shape, while the severing enzyme Katanin facilitates network remodelling to ensure tissue-wide cell size homeostasis. During fold initiation, Patronin redistributes following basal polarity shifts in the initiating cells, apparently weakening the scaffolding forces to allow dome descent. The homeostatic network that ensures size/shape homogeneity is thus repurposed for cell shortening, linking epithelial polarity to folding via a microtubule-based mechanical mechanism.

Highlights d Btd/Eve-dependent lateral MyoII shortens cells to initiate CF d Single-cell row Btd/Eve positional code accounts for only 80% of CF-initiating cells d Mis-specification arises due to MyoII noise, and yet the cells align among themselves d Mechanical coupling via planar polarized MyoII aligns cells to ensure CF linearity

The dynamics of extracellular signal-regulated kinase (ERK) signaling underlies its versatile functions in cell differentiation, cell proliferation, and cell motility. Classical studies in Drosophila established that a gradient of epidermal growth factor receptor (EGFR)-ERK signaling is essential for these cellular responses. However, we challenge this view by the real-time monitoring of ERK activation; we show that a switch-like ERK activation is essential for the invagination movement of the Drosophila tracheal placode. This switch-like ERK activation stems from the positive feedback regulation of the EGFR-ERK signaling and a resultant relay of EGFR-ERK signaling among tracheal cells. A key transcription factor Trachealess (Trh) permissively regulates the iteration of the relay, and the ERK activation becomes graded in trh mutant. A mathematical model based on these observations and a molecular link between ERK activation dynamics and myosin shows that the relay mechanism efficiently promotes epithelial invagination while the gradient mechanism does not.

Human iPS cell (iPSC)-derived cardiomyocytes (CMs) hold promise for drug discovery for heart diseases and cardiac toxicity tests. To utilize human iPSC-derived CMs, the establishment of three-dimensional (3D) heart tissues from iPSC-derived CMs and other heart cells, and a sensitive bioassay system to depict physiological heart function are anticipated. We have developed a heart-on-a-chip microdevice (HMD) as a novel system consisting of dynamic culture-based 3D cardiac microtissues derived from human iPSCs and microelectromechanical system (MEMS)-based microfluidic chips. The HMDs could visualize the kinetics of cardiac microtissue pulsations by monitoring particle displacement, which enabled us to quantify the physiological parameters, including fluidic output, pressure, and force. The HMDs demonstrated a strong correlation between particle displacement and the frequency of external electrical stimulation. The transition patterns were validated by a previously reported versatile video-based system to evaluate contractile function. The patterns are also consistent with oscillations of intracellular calcium ion concentration of CMs, which is a fundamental biological component of CM contraction. The HMDs showed a pharmacological response to isoproterenol, a β-adrenoceptor agonist, that resulted in a strong correlation between beating rate and particle displacement. Thus, we have validated the basic performance of HMDs as a resource for human iPSC-based pharmacological investigations.

Highlights d Nanopores of Drosophila olfactory sensillum are modified cuticular envelope d Endocytic membrane structures are associated with the site of nanopore formation d Gore-tex/Osiris23 endosomal protein is required for nanopore formation d gore-tex/Osiris23 mutants showed greatly reduced olfactory response

Cortical spreading depression (SD) is propagating neuronal and glial depolarization and is thought to underly the pathophysiology of migraine. We have reported that cortical SD facilitates the proliferative activity of NG2-containing progenitor cells (NG2 cells) that give rise to oligodendrocytes and immature neurons under the physiological conditions in the adult mammalian cortex. Astrocytes have an important role in the maintenance of neuronal functions and alleviate neuronal damage after intense neuronal excitation, including SD and seizures. We here investigated whether SD promotes astrocyte generation from NG2 cells following SD stimuli. Spreading depression was induced by epidural application of 1 mol/L KCl solution in adult rats. We investigated the cell fate of NG2 cells following SD-induced proliferation using 5 0 -bromodeoxyuridine labeling and immunohistochemical analysis. Newly generated astrocytes were observed only in the SD-stimulated cortex, but not in the contralateral cortex or in normal cortex. The astrocytes were generated from proliferating NG2 cells. Astrogenesis depended on the number of SD stimuli, and was accompanied by suppression of oligodendrogenesis. These observations indicate that the cell fate of NG2 cells was shifted from oligodendrocytes to astrocytes depending on SD stimuli, suggesting activitydependent tissue remodeling for maintenance of brain functions.

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