During mammalian development, neuroepithelial cells function as mitotic progenitors, which self-renew and generate neurons. Although spindle orientation is important for such polarized cells to undergo symmetric or asymmetric divisions, its role in mammalian neurogenesis remains unclear. Here we show that control of spindle orientation is essential in maintaining the population of neuroepithelial cells, but dispensable for the decision to either proliferate or differentiate. Knocking out LGN, (the G protein regulator), randomized the orientation of normally planar neuroepithelial divisions. The resultant loss of the apical membrane from daughter cells frequently converted them into abnormally localized progenitors without affecting neuronal production rate. Furthermore, overexpression of Inscuteable to induce vertical neuroepithelial divisions shifted the fate of daughter cells. Our results suggest that planar mitosis ensures the self-renewal of neuroepithelial progenitors by one daughter inheriting both apical and basal compartments during neurogenesis.

Mouse NEAT1 is required for paraspeckle formation in a subset of cells but is not essential for animal health and viability.

Malat1 is an abundant long, noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous studies in cell culture have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine-and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-knockout (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long, noncoding RNA-Neat1-which is an architectural component of nuclear bodies known as paraspeckles, were down-regulated in a particular set of tissues and cells lacking Malat1. We propose that Malat1 is not essential in living mice maintained under normal laboratory conditions and that its function becomes apparent only in specific cell types and under particular conditions.

Posttranscriptional regulation of IL-6 has been largely uncharacterized, with the exception of the ribonuclease Regnase-1, which prevents autoimmunity by destabilizing IL-6 mRNA. Here, we identified AT-rich interactive domain-containing protein 5A (Arid5a) as a unique RNA binding protein, which stabilizes IL-6 but not TNF-α mRNA through binding to the 3′ untranslated region of IL-6 mRNA. Arid5a was enhanced in macrophages in response to LPS, IL-1β, and IL-6. Arid5a deficiency inhibited elevation of IL-6 serum level in LPStreated mice and suppressed IL-6 levels and the development of T H 17 cells in experimental autoimmune encephalomyelitis. Importantly, Arid5a inhibited the destabilizing effect of Regnase-1 on IL-6 mRNA. These results indicate that Arid5a plays an important role in promotion of inflammatory processes and autoimmune diseases.immune regulation | RNA-protein complex

Summary: A series of conditional reporter mouse lines were established in which specific organelles were labeled with fluorescent proteins. Subcellular localization and intensity of 28 fluorescent fusion-protein constructs were surveyed in cell lines, and 16 constructs then were selected to generate mouse lines. The fusion cDNAs were inserted into the ROSA26 genomic locus next to the stop sequences flanked with loxP so that fluorescent proteins were expressed under the ubiquitous ROSA26 transcriptional machinery when the loxP sequences were recombined with Cre. The subcellular localization and intensity of the fusion product in each reporter mouse line were examined by ubiquitously expressing them in E7.5 embryos. Twelve reporter lines, that mark nucleus, mitochondria, Golgi apparatus, plasma membrane, microtubule, actin filament, and focal adhesion, were found suitable for live imaging. Distinct double staining was demonstrated for nucleus and plasma membrane or Golgi apparatus; clear time-lapse live images were obtained for nucleus and plasma membranes; conditional expression was confirmed on Lyn-Venus and H2B-mCherry lines in notochord with Not-Cre. genesis 49:579-590, 2011. V V C 2011 Wiley-Liss, Inc.