An Organoid-Based Model of Cortical Development Identifies Non-Cell-Autonomous Defects in Wnt Signaling Contributing to Miller-Dieker Syndrome.

Miller-Dieker syndrome (MDS) is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE (coding for 14.3.3ε) and leads to malformations during cortical development. Here, we used patient-specific forebrain-type organoids to investigate pathological changes associated with MDS. Patient-derived organoids are significantly reduced in size, a change accompanied by a switch from symmetric to asymmetric cell division of ventricular zone radial glia cells (vRGCs). Alterations in microtubule network organization in vRGCs and a disruption of cortical niche architecture, including altered expression of cell adhesion molecules, are also observed. These phenotypic changes lead to a non-cell-autonomous disturbance of the N-cadherin/ß-catenin signaling axis. Reinstalling active ß-catenin signaling rescues division modes and ameliorates growth defects. Our data define the role of LIS1 and 14.3.3ε in maintaining the cortical niche and highlight the utility of organoid-based systems for modeling complex cell-cell interactions in vitro.

The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells.

Stem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. Drosophila neural stem cells (NSCs) are quiescent at early larval stages, when they are reactivated in response to metabolic changes. Here we report that cell-contact inhibition of growth through the canonical Hippo signalling pathway maintains NSC quiescence. Loss of the core kinases hippo or warts leads to premature nuclear localization of the transcriptional co-activator Yorkie and initiation of growth and proliferation in NSCs. Yorkie is necessary and sufficient for NSC reactivation, growth and proliferation. The Hippo pathway activity is modulated via inter-cellular transmembrane proteins Crumbs and Echinoid that are both expressed in a nutrient-dependent way in niche glial cells and NSCs. Loss of crumbs or echinoid in the niche only is sufficient to reactivate NSCs. Finally, we provide evidence that the Hippo pathway activity discriminates quiescent from non-quiescent NSCs in the Drosophila nervous system.

Trees as huge flowers and flowers as oversized floral guides: the role of floral color change and retention of old flowers in Tibouchina pulchra.

Floral color changes and retention of old flowers are frequently combined phenomena restricted to the floral guide or single flowers in few-flowered inflorescences. They are thought to increase the attractiveness over long distances and to direct nearby pollinators toward the rewarding flowers. In Tibouchina pulchra, a massively flowering tree, the whole flower changes its color during anthesis. On the first day, the flowers are white and on the next 3 days, they change to pink. This creates a new large-scale color pattern in which the white pre-changed flowers contrast against the pink post-changed ones over the entire tree. We describe the spectral characteristics of floral colors of T. pulchra and test bumblebees' response to this color pattern when viewed at different angles (simulating long and short distances). The results indicated the role of different color components in bumblebee attraction and the possible scenario in which this flower color pattern has evolved. We tested bumblebees' preference for simulated trees with 75% pink and 25% white flowers resembling the color patterns of T. pulchra, and trees with green leaves and pink flowers (control) in long-distance approach. We also compared an artificial setting with three pink flowers and one white flower (T. pulchra model) against four pink flowers with white floral guides (control) in short-distance approach. Bumblebees spontaneously preferred the simulated T. pulchra patterns in both approaches despite similar reward. Moreover, in short distances, pollinator visits to peripheral, non-rewarding flowers occurred only half as frequently in the simulated T. pulchra when compared to the control. Thefore, this exceptional floral color change and the retention of old flowers in T. pulchra favors the attraction of pollinators over long distances in a deception process while it honestly directs them toward the rewarding flowers at short distances possibly exploring their innate color preferences.