The regulation of asymmetric cell division (ACD) during corticogenesis is incompletely understood. We document that spindle-size asymmetry (SSA) between the two poles occurs during corticogenesis and parallels ACD. SSA appears at metaphase and is maintained throughout division, and we show it is necessary for proper neurogenesis. Imaging of spindle behavior and division outcome reveals that neurons preferentially arise from the larger-spindle pole. Mechanistically, SSA magnitude is controlled by Wnt7a and Vangl2, both members of the Wnt/planar cell polarity (PCP)-signaling pathway, and relayed to the cell cortex by P-ERM proteins. In vivo, Vangl2 and P-ERM downregulation promotes early cell-cycle exit and prevents the proper generation of late-born neurons. Thus, SSA is a core component of ACD that is conserved in invertebrates and vertebrates and plays a key role in the tight spatiotemporal control of self-renewal and differentiation during mammalian corticogenesis.

The question of how neurons and glial cells are generated during the development of the CNS has over time led to two alternative models: either neuroepithelial cells are capable of giving rise to neurons first and to glial cells at a later stage (switching model), or they are intrinsically committed to generate one or the other (segregating model). Using the developing diencephalon as a model and by selecting a subpopulation of ventricular cells, we analyzed both in vitro, using clonal analysis, and in vivo, using inducible Cre/loxP fate mapping, the fate of neuroepithelial and radial glial cells generated at different time points during embryonic development. We found that, during neurogenic periods [embryonic day 9.5 (E9.5) to 12.5], proteolipid protein ( plp)-expressing cells were lineage-restricted neuronal precursors, but later in embryogenesis, during gliogenic periods (E13.5 to early postnatal), plp-expressing cells were lineage-restricted glial precursors. In addition, we show that glial cells forming at E13.5 arise from a new pool of neuroepithelial progenitors distinct from neuronal progenitors cells, which lends support to the segregating model.

A large prototype of 1.3 m 3 was designed and built as a demonstrator of the semi-digital hadronic calorimeter (SDHCAL) concept proposed for the future ILC experiments. The prototype is a sampling hadronic calorimeter of 48 units. Each unit is built of an active layer made of 1 m 2 Glass Resistive Plate Chamber (GRPC) detector placed inside a cassette whose walls are made of stainless steel. The cassette contains also the electronics used to read out the GRPC detector. The lateral granularity of the active layer is provided by the electronics pick-up pads of 1 cm 2 each. The cassettes are inserted into a self-supporting mechanical structure built also of stainless steel plates which, with the cassettes walls, play the role of the absorber. The prototype was designed to be very compact and important efforts were made to minimize the number of services cables to optimize the efficiency of the Particle Flow Algorithm techniques to be used in the future ILC experiments. The different components of the SDHCAL prototype were studied individually and strict criteria were applied for the final selection of these components. Basic calibration procedures were performed after the prototype assembling. The prototype is the first of a series of new-generation detectors equipped with a power-pulsing mode intended to reduce the power consumption of this highly granular detector. A dedicated acquisition system was developed to deal with the output of more than 440000 electronics channels in both trigger and triggerless modes. After its completion in 2011, the prototype was commissioned using cosmic rays and particles beams at CERN.