Mammalian Neurogenesis Requires Treacle-Plk1 for Precise Control of Spindle Orientation, Mitotic Progression, and Maintenance of Neural Progenitor Cells

The cerebral cortex is a specialized region of the brain that processes cognitive, motor, somatosensory, auditory, and visual functions. Its characteristic architecture and size is dependent upon the number of neurons generated during embryogenesis and has been postulated to be governed by symmetric versus asymmetric cell divisions, which mediate the balance between progenitor cell maintenance and neuron differentiation, respectively. The mechanistic importance of spindle orientation remains controversial, hence there is considerable interest in understanding how neural progenitor cell mitosis is controlled during neurogenesis. We discovered that Treacle, which is encoded by the Tcof1 gene, is a novel centrosome- and kinetochore-associated protein that is critical for spindle fidelity and mitotic progression. Tcof1/Treacle loss-of-function disrupts spindle orientation and cell cycle progression, which perturbs the maintenance, proliferation, and localization of neural progenitors during cortical neurogenesis. Consistent with this, Tcof1+/− mice exhibit reduced brain size as a consequence of defects in neural progenitor maintenance. We determined that Treacle elicits its effect via a direct interaction with Polo-like kinase1 (Plk1), and furthermore we discovered novel in vivo roles for Plk1 in governing mitotic progression and spindle orientation in the developing mammalian cortex. Increased asymmetric cell division, however, did not promote increased neuronal differentiation. Collectively our research has therefore identified Treacle and Plk1 as novel in vivo regulators of spindle fidelity, mitotic progression, and proliferation in the maintenance and localization of neural progenitor cells. Together, Treacle and Plk1 are critically required for proper cortical neurogenesis, which has important implications in the regulation of mammalian brain size and the pathogenesis of congenital neurodevelopmental disorders such as microcephaly

Standards for reporting randomized controlled trials in neurosurgery

Object The Consolidated Standards for Reporting of Trials (CONSORT) criteria were published in 1996 to standardize the reporting and improve the quality of clinical trials. Despite having been endorsed by major medical journals and shown to improve the quality of reported trials, neurosurgical journals have yet to formally adopt these reporting criteria. The purpose of this study is to evaluate the quality and reporting of randomized controlled trials (RCTs) in neurosurgery and the factors that may affect the quality of reported trials. Methods The authors evaluated all neurosurgical RCTs published in 2006 and 2007 in the principal neurosurgical journals (Journal of Neurosurgery; Neurosurgery; Surgical Neurology; Journal of Neurology, Neurosurgery, and Psychiatry; and Acta Neurochirurgica) and in 3 leading general medical journals (Journal of the American Medical Association, Lancet, and the New England Journal of Medicine). Randomized controlled trials that addressed operative decision making or the treatment of neurosurgical patients were included in this analysis. The RCT quality was evaluated using the Jadad score and the CONSORT checklist. Results In 2006 and 2007, 27 RCTs relevant to intracranial neurosurgery were reported. Of these trials, only 59% had a Jadad score ≥ 3. The 3 major medical journals all endorsed the CONSORT guidelines, while none of the neurosurgical journals have adopted these guidelines. Randomized controlled trials published in the 3 major medical journals had a significantly higher mean CONSORT score (mean 41, range 39–44) compared with those published in neurosurgical journals (mean 26.4, range 17–38; p < 0.0001). Jadad scores were also significantly higher for the major medical journals (mean 3.42, range 2–5) than neurosurgical journals (mean 2.45, range 1–5; p = 0.05). Conclusions Despite the growing volume of RCTs in neurosurgery, the quality of reporting of these trials remains suboptimal, especially in the neurosurgical journals. Improved awareness of the CONSORT guidelines by journal editors, reviewers, and authors of these papers could improve the methodology and reporting of RCTs in neurosurgery

Germination responses of four native terrestrial orchids from south-west Western Australia to temperature and light treatments

We report an investigation into the impact of temperature and illumination on in vitro symbiotic and asymbiotic germination of the threatened taxon Caladenia huegelii, and three other orchid spp. namely—Caladenia latifolia, Microtis media and Pterostylis sanguinea, all species from south-west Western Australia, a recognized biodiversity hotspot. High symbiotic germination on oatmeal agar (OMA + fungal symbionts specific to each species) was recorded in three species in continuous dark incubation i.e. C. huegelii seeds (98 % germination at 25 °C), and M. media and P. sanguinea (93 and 98 % respectively at 20 °C). Highest symbiotic germination for C. latifolia (100 %) was observed at 15 and 20 °C under light treatment (12/12 h light/dark). Low temperature incubation (10 °C) significantly suppressed symbiotic germination/development of seedlings across all species. Asymbiotic media treatments assessed (OMA minus fungal symbionts, Pa5 and ½ MS), failed to stimulate any germination with C. latifolia seeds at 20 °C in either light or dark treatments after an 8 week incubation period. Seeds of M. media sown onto ½ MS medium resulted in higher germination in all developmental stages (3–5) in dark treatment than OMA and Pa5. Seeds of P. sanguinea sown onto ½ MS medium resulted in higher overall germination in all developmental stages (3–5) in light and dark incubation compared to OMA and Pa5. OMA supported the highest asymbiotic germination (100 %) in both light and dark incubation with M. media (only to stage 3) but did not support germination and development with other spp. tested.Caladenia huegelii seeds reached developmental Stage 3 (i.e. germinated), but only on Pa5 medium and only at a relatively low rate in either light (2.6 %) or dark (2.1 %). Germination was higher and development of seedlings faster overall in all test species in symbiotic compared with asymbiotic media treatments. P. sanguinea seeds demonstrated the best response (among species tested) to asymbiotic germination on ½ MS with 40–53 % of germinated seeds spread over developmental stages 3–5 in light or dark incubation (at 20 °C) respectively. Illumination had no effect on fungal symbiont growth across all species, however incubation temperature treatments (10, 15, 20 and 25 °C) affected fungal growth rate. Growth of the fungal symbionts of C. huegelii, M. media and C. latifolia demonstrated significantly lower activity at 10 °C, but the cumulative radial growth rate of the P. sanguinea fungal symbiont reached 64 cm2 after only 2 weeks at all temperatures tested, including 10 °C. The study highlights differences in symbiotic and aysmbiotic germination and early protocorm development in vitro between co-occurring herbaceous terrestrial Australian orchid taxa in response to variations in basal media, temperature and light