The human-specific gene FRMPD2B couples postnatal experience to the expansion of cortical connectivity

The human neocortex undergoes an extended postnatal development, during which experiences shape neuronal circuits, a crucial factor in human cognitive abilities. The origin of this unique brain development process has been unclear, particularly in terms of human-specific genetic factors that influence it. In this study, researchers discovered the human-specific gene FRMPD2B, which regulates cortical connectivity in response to activity and experience.

FRMPD2B is primarily expressed in specific neurons found in areas where cortical projections occur, both during infancy and childhood. This gene plays a role in promoting the growth of dendrites, axons, and synapses, and is necessary for the proper development of these human cortical neurons when transplanted into other organisms.

FRMPD2B expression is influenced by both activity and experience, with this regulatory mechanism becoming more sophisticated after a partial duplication of the gene and a retrotransposon insertion that altered its promoter region. These findings provide insights into how a series of genetic changes have resulted in a unique human-specific developmental program that enables postnatal experiences to expand cortical connectivity, thereby connecting genome evolution to human brain plasticity.