Hominini-specific regulation of CBLN2 increases prefrontal spinogenesis.

The similarities and differences between nervous systems of various species result from developmental constraints and specific adaptations. Comparative analyses of the prefrontal cortex (PFC), a cerebral cortex region involved in higher-order cognition and complex social behaviours, have identified true and potential human-specific structural and molecular specializations, such as an exaggerated PFC-enriched anterior-posterior dendritic spine density gradient. These changes are probably mediated by divergence in spatiotemporal gene regulation, which is particularly prominent in the midfetal human cortex.

Regulation of prefrontal patterning and connectivity by retinoic acid.

The prefrontal cortex (PFC) and its connections with the mediodorsal thalamus are crucial for cognitive flexibility and working memory and are thought to be altered in disorders such as autism and schizophrenia. Although developmental mechanisms that govern the regional patterning of the cerebral cortex have been characterized in rodents, the mechanisms that underlie the development of PFC-mediodorsal thalamus connectivity and the lateral expansion of the PFC with a distinct granular layer 4 in primates remain unknown. Here we report an anterior (frontal) to posterior (temporal), PFC-enriched gradient of retinoic acid, a signalling molecule that regulates neural development and function, and we identify genes that are regulated by retinoic acid in the neocortex of humans and macaques at the early and middle stages of fetal development.

The evolution of the human brain and disease susceptibility.

Evolutionary perspective is critical for understanding human biology, human medicine, and the traits that make human beings unique. One of the crucial characteristics that sets humans apart from other extant species is our cognitive ability, which allows for complex processes including symbolic thought, theory of mind, and syntactical-grammatical language, and is thought to arise from the expansion and specialization of the human nervous system. It has been hypothesized that the same evolutionary changes that allowed us to develop these valuable skills made humans susceptible to neurodevelopmental and neurodegenerative disease.

Modeling the Evolution of Human Brain Development Using Organoids.

In a recent issue of Nature, Kanton et al. explore human brain evolution and development by profiling the single-cell transcriptomes and epigenomes of cerebral organoids derived from human, chimpanzee, and macaque stem cells. Their results reveal key molecular characteristics that differentiate humans and non-human primates at the earliest stages of brain development.

A statistical framework for cross-tissue transcriptome-wide association analysis.

Transcriptome-wide association analysis is a powerful approach to studying the genetic architecture of complex traits. A key component of this approach is to build a model to impute gene expression levels from genotypes by using samples with matched genotypes and gene expression data in a given tissue. However, it is challenging to develop robust and accurate imputation models with a limited sample size for any single tissue.