Despite the well established role of the frontal and posterior perisylvian cortices in many facets of human-cognitive specializations, including language, little is known about the developmental patterning of these regions in the human brain. We performed a genome-wide analysis of human cerebral patterning during midgestation, a critical epoch in cortical regionalization. A total of 345 genes were identified as differentially expressed between superior temporal gyrus (STG) and the remaining cerebral cortex. Gene ontology categories representing transcription factors were enriched in STG, whereas cell-adhesion and extracellular matrix molecules were enriched in the other cortical regions. Quantitative RT-PCR or in situ hybridization was performed to validate differential expression in a subset of 32 genes, most of which were confirmed. LIM domain-binding 1 ( LDB1 ), which we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4 ( LMO4 ), a gene known to be involved in the asymmetric pattering of the perisylvian region in the developing human brain. Protocadherin 17 ( PCDH17 ), a neuronal cell adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex. Contactin associated protein-like 2 ( CNTNAP2 ), in which mutations are known to cause autism, epilepsy, and language delay, showed a remarkable pattern of anterior-enriched cortical expression in human that was not observed in mouse or rat. These data highlight the importance of expression analysis of human brain and the utility of cross-species comparisons of gene expression. Genes identified here provide a foundation for understanding molecular aspects of human-cognitive specializations and the disorders that disrupt them.

The tumour suppressor p53 is a crucial regulator of cell cycle arrest and apoptosis by acting as a transcription factor to regulate a variety of genes. At least in part, this control is exerted by p53 via regulating expression of numerous microRNAs. We identified two abundantly expressed microRNAs, miR-16 and miR-26a, whose expression is regulated by p53 during the checkpoint arrest induced by the genotoxic drug, doxorubicin. Importantly, among the targets of these miRs are two critical checkpoint kinases, Chk1 and Wee1. The p53-dependent augmentation of miR-16 and miR-26a expression levels led to the cell cycle arrest of tumour cells in G1/S and increased apoptosis. Strikingly, the bioinformatics analysis of survival times for patients with breast and prostate cancers has revealed that co-expression of mir-16 and miR-26a correlated with a better survival outcome. Collectively, our data provide a novel mechanism whereby p53 represses Chk1 and Wee1 expression, at least partially, via upregulation of miR-16 and miR-26a and thus sensitizes tumour cells to genotoxic therapies.

KMT Set7/9 affects genotoxic stress response via the Mdm2 axis