Osteocyte transcriptome mapping identifies a molecular landscape controlling skeletal homeostasis and susceptibility to skeletal disease.

Osteocytes are master regulators of the skeleton. We mapped the transcriptome of osteocytes from different skeletal sites, across age and sexes in mice to reveal genes and molecular programs that control this complex cellular-network. We define an osteocyte transcriptome signature of 1239 genes that distinguishes osteocytes from other cells. 77% have no previously known role in the skeleton and are enriched for genes regulating neuronal network formation, suggesting this programme is important in osteocyte communication. We evaluated 19 skeletal parameters in 733 knockout mouse lines and reveal 26 osteocyte transcriptome signature genes that control bone structure and function. We showed osteocyte transcriptome signature genes are enriched for human orthologs that cause monogenic skeletal disorders (P = 2.4 × 10-22) and are associated with the polygenic diseases osteoporosis (P = 1.8 × 10-13) and osteoarthritis (P = 1.6 × 10-7). Thus, we reveal the molecular landscape that regulates osteocyte network formation and function and establish the importance of osteocytes in human skeletal disease

Synthesis and thermal stability of cis-dichloro[(E)-ethyl-2-(2-((8-hydroxyquinolin-2-il)methylene)hidrazinyl)acetate-kappa(2) N]-palladium(II) complex

The structure of new cis-dichloro[(E)-ethyl-2-(2-((8-hydroxyquinolin-2-il)methylene)hidrazinyl)acetate-kappa(2) N]-palladium(II) complex was determined using a combination of XRD and IR measurements and DFT calculations. Inherent flexibility of its structure is evident from the complexity of its IR spectrum, which could only be theoretically reproduced as a combination of several closely related structures, involving rotation around C-O bond and changes in hydrogen interactions of its -OH group. Its thermal stability and decomposition were studied non-isothermally, and the thermal decomposition mechanism was proposed using correlation with DFT calculations at the molecular level. It was determined that the initial degradation step consists of the release of Cl free radical, which then reacts with both the initial compound and the degradation products. Besides the endothermic steps, there are exothermic ones, contributing to the complex shape of the DSC curve, consisted of overlapping endothermic and exothermic peaks. Deconvolution of DTG curve allowed identification of primary fragments of the initial degradation process and, in conjunction with DFT calculations, construction of the most likely reaction mechanism

TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons

International audienceTSHZ3, which encodes a zinc-finger transcription factor, was recently positioned as a hub gene in a module of the genes with the highest expression in the developing human neocortex, but its functions remained unknown. Here we identify TSHZ3 as the critical region for a syndrome associated with heterozygous deletions at 19q12-q13.11, which includes autism spectrum disorder (ASD). In Tshz3-null mice, differentially expressed genes include layer-specific markers of cerebral cortical projection neurons (CPNs), and the human orthologs of these genes are strongly associated with ASD. Furthermore, mice heterozygous for Tshz3 show functional changes at synapses established by CPNs and exhibit core ASD-like behavioral abnormalities. These findings highlight essential roles for Tshz3 in CPN development and function, whose alterations can account for ASD in the newly defined TSHZ3 deletion syndrome