The different modes of stem cell division are tightly regulated to balance growth and differentiation during organ development and homeostasis, and these regulatory processes are subverted in tumor formation. Here, we developed markers that provided the single-cell resolution necessary to quantify the three modes of division taking place in the developing nervous system in vivo: self-expanding, PP; self-replacing, PN; and self-consuming, NN. Using these markers and a mathematical model that predicts the dynamics of motor neuron progenitor division, we identify a role for the morphogen Sonic hedgehog in the maintenance of stem cell identity in the developing spinal cord. Moreover, our study provides insight into the process linking lineage commitment to neurogenesis with changes in cell-cycle parameters. As a result, we propose a challenging model in which the external Sonic hedgehog signal dictates stem cell identity, reflected in the consequent readjustment of cell-cycle parameters.

The activity level of the BMP effectors SMAD1/5 dictates whether stem cell divisions are self-expanding, self-renewing, or self-consuming during spinal interneuron generation.

Tight control of the balance between self-expanding symmetric and self-renewing asymmetric neural progenitor divisions is crucial to regulate the number of cells in the developing central nervous system. We recently demonstrated that Sonic hedgehog (Shh) signalling is required for the expansion of motor neuron progenitors by maintaining symmetric divisions. Here we show that activation of Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions. Notably, Shh signalling upregulates the expression of pericentrin, which is required to dock PKA to the centrosomes, which in turn exerts a positive feedback onto Shh signalling. Thus, by controlling centrosomal protein assembly, we propose that Shh signalling overcomes the intrinsic asymmetry at the centrosome during neuroepithelial cell division, thereby promoting self-expanding symmetric divisions and the expansion of the progenitor pool.

E-mail adress: nguyen@tagc.univ-mrs.fr (C Nguyen). * ManuscriptHAL author manuscript inserm-00276188, version 1 HAL author manuscript Experimental Cell Research 2007;313(3):614-26 2 AbstractSpatial gene is expressed in highly polarized cell types, such as epithelial cells in the thymus, neurons in the brain and germ cells in the testis. In this study, we report the characterization and the distribution of Spatial proteins during mouse spermatogenesis. Besides Spatial-ε and -δ, we show that the newly described short isoform Spatial-β is expressed specifically in round spermatids. Using indirect immunofluorescence, we detected Spatial in the cytosol of early round spermatid. By the end stages of round spermatids, Spatial is concentrated at the opposite face of the acrosome near the nascent flagellum and in the manchette during the elongation process.Finally in mature sperm, Spatial persists in the principal piece of the tail. Moreover, we found that Spatial colocalizes with KIF17b, a testis-specific isoform of the brain kinesin motor KIF17.This colocalization is restricted to the manchette and the principal piece of the sperm tail. Further, coimmunoprecipitation experiments of native proteins from testis lysate confirmed SpatialKIF17b association through Spatial-ε long isoform. Together, these findings imply a function of Spatial in spermatid differentiation as being a new cargo of the kinesin KIF17b in a microtubuledependent mechanism specific to the manchette and the principal piece of the sperm tail.