BackgroundPrecise spatiotemporal control of gene expression is essential for the establishment of correct cell numbers and identities during brain development. This process involves epigenetic control mechanisms, such as those mediated by the polycomb group protein Ezh2, which catalyzes trimethylation of histone H3K27 (H3K27me3) and thereby represses gene expression.ResultsHerein, we show that Ezh2 plays a crucial role in the development and maintenance of the midbrain. Conditional deletion of Ezh2 in the developing midbrain resulted in decreased neural progenitor proliferation, which is associated with derepression of cell cycle inhibitors and negative regulation of Wnt/β-catenin signaling. Of note, Ezh2 ablation also promoted ectopic expression of a forebrain transcriptional program involving derepression of the forebrain determinants Foxg1 and Pax6. This was accompanied by reduced expression of midbrain markers, including Pax3 and Pax7, as a consequence of decreased Wnt/β-catenin signaling.ConclusionEzh2 is required for appropriate brain growth and maintenance of regional identity by H3K27me3-mediated gene repression and control of canonical Wnt signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-015-0210-9) contains supplementary material, which is available to authorized users.

Background: The subchondral lamella of the sacroiliac joint (SIJ) auricular surface is morphologically inconsistent, varying inter-individually and side-dependently. These variations have been well documented, however, the morpho-mechanical relationship to sacroiliac joint dysfunction (SIJD) remains unstudied to date. Here, the bone mineralisation density of the iliac and sacral auricular surface subchondral endplate is compared between morphological subtypes, as well as in large and small surfaces, in a cohort comprising SIJD joints and controls.Methods: Computed tomography (CT) datasets from 29 patients with bilateral or unilateral SIJD were subjected to CT osteoabsorptiometry. Sacral and iliac surface areas and posterior angles were calculated and surfaces were classi ed into small (<15 cm 3 ) and large (≥15 cm 3 ) joints and morphological types 1 (>160°), 2 (130-160°) and 3 (<130°), respectively. Mineralisation patterns were classi ed into four patterns, two marginal (M1 and M2) and two non-marginal (N1 and N2). Each sacral and iliac surface was subsequently classi ed into one of these mineralisation groups.Results: The surface area of all joints in the cohort averaged 15.0±2.4 cm 2 (males 16.2±2.5 cm 2 , females 13.7±1.6 cm 2 ). No age correlations with surface area were found nor differences in mean HU values when comparing sizes, sexes or morphology type when looking at painful joints (unilateral or bilateral) and contralateral non-painful joints. Comparisons of controls with the SIJD cohort revealed signi cant differences in female sacra (p=0.02) and small sacra (p=0.03). There was low conformity in marginal and non-marginal patterns, 26% for contralateral non-painful joints, and 46% conformity in painful joints.The majority of dysfunctional joints was of type 2 morphology (59%), equally distributed between small (49%) and large joints (51%). Larger joints had the highest frequency of painful joints (72%). Regarding the prominence of sub-patterns, M1C was more prominent in painful joints.Conclusions: Load distribution related to difference in auricular surface morphology seems to have little impact on pain-related subchondral bone adaptation in cases of SIJD. Larger joints may be predisposed to the onset of pain due to the weakening of the extracapsular structures. Pain-affected joints re ect common conformity patterns of sacral apex mineralisation with corresponding superior corner iliac mineralisation.

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Background Bone functional adaptation rationalises the inhomogeneous morphology found in bone. By means of computed tomography osteoabsorptiometry and micro-computed tomography, the mineralisation of the subchondral endplates and trabecular microstructure of vertebral bodies can be assessed to visualise the chronic loading conditions bone endures over time. In this study, we determined cancellous and compartment-specific trabecular architecture in the cervical vertebra to aid with successful integration of orthopaedic implants. Methods We examined the micro-computed tomography scans of seven prospectively healthy C4 vertebrae, evaluated their microstructure parameters (bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number per volume (Tb.N), connectivity density (Conn.D), structure model index (SMI), and degree of anisotropy (DA), and compared the trabecular architecture in twelve predefined volumes of interest: the cranial and caudal 0–10%, 10–15%, and 25–50% in both the ventral and dorsal half. Using computed tomography osteoabsorptiometry, the subchondral bone mineralisation of the subchondral endplates of nine C4 vertebrae was also evaluated. Results Highest mineralisation is located dorsally at the endplates. Tb.Sp and Tb.N were the only two parameters that displayed significant differences in averaged values of VOI. Nonetheless, distinct, consistent ventral–dorsal modulations were seen in matched sample ventral–dorsal comparison in the BV/TV, BS/BV, and SMI overall levels, as well as in Tb.Th in the three caudal levels. To simplify, the vertebra was split into ventral–cranial, dorsal–cranial, ventral–caudal, and dorsal–caudal equal quarters. The ventral quarters display lower BV/TV, respectively, higher BS/BV and SMI than their sample paired dorsal quarters. The ventral–cranial quarter shows the lowest BV/TV and the highest BS/BV and SMI, describing spacious cancellous bone with rod-like trabeculae. In contrast, the dorsal–caudal quarter exhibits the highest BV/TV and Tb.Th and the lowest BS/BV and SMI, illustrating thicker, denser, and more plate-like trabeculae. The dorsal–cranial and ventral–caudal quarters are comparable and represent intermediate characteristics. Conclusions CT-OAM and µCT demonstrate the interdependence of compact and trabecular bone in response to long-term loading conditions. Results show highest mineralisation in the dorso-caudal part of the C4 vertebra. Recommended placement of orthopaedic implants should be positioned dorsally with screws anchored in the dorsal–caudal region.

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