However, in our study, the ratio of excitatory to inhibitory synapse markers was not completely PHA-680632 restored, suggesting that additional orthologous Hsa21 genes may be involved in this imbalance. Indeed, it has been shown that triplication of the Olig1 and Olig2 genes, which are also in Hsa21, is also implicated in the increased number of inhibitory neurons found in the forebrains of TS mice, which is accompanied by an increase in spontaneous inhibitory postsynaptic currents in pyramidal neurons in the CA1 area. Several studies have associated Dyrk1A gene dosage with brain volume ; however, consistent with the lack of an effect of normalization of the Dyrk1A copy number on the density of mature granule neurons, in this study, normalization of the Dyrk1A gene dosage did not affect the DG volume, the SGZ area or the body weight of TS animals, suggesting that other genes may be involved in these developmental alterations. Thus, the present results support the notion that Dyrk1A gene dosage plays a role in some of the functional, but not the structural, alterations detected in the TS mouse. Hox genes encode evolutionarily conserved transcription factors that control the formation of body segment-specific structures by regulating the transcription of downstream effectors that, in turn, direct the morphogenetic events leading to the complex body forms along the embryonic axes in metazoan. Consequently, mutations in Hox genes alter segmental identity and cause VX-765 morphological defects. In mammals, 39 Hox genes are distributed over four clusters, each containing 9 to 11 genes closely packed in less than 150-kb of sequences. Their spatio-temporal expression profile during embryogenesis reflects their arrangement in the clusters: the 39 most genes are expressed earlier and their expression domain reaches a more anterior limit than those occupying 59 positions. As a result, members of the Hox complexes are expressed in nested and overlapping domains along the developing body suggesting that specific combinations of HOX proteins provide a unique address to defined regions. Based on sequence homology and location within clusters, Hox genes are also classified into 13 paralog groups.