The human-specific paralogs SRGAP2B and SRGAP2C differentially modulate SRGAP2A-dependent synaptic development.

ABSTRACT: Human-specific gene duplications (HSGDs) have recently emerged as key modifiers of brain development and evolution. However, the molecular mechanisms underlying the function of HSGDs remain often poorly understood. In humans, a truncated duplication of SRGAP2A led to the emergence of two human-specific paralogs: SRGAP2B and SRGAP2C. The ancestral copy SRGAP2A limits synaptic density and promotes maturation of both excitatory (E) and inhibitory (I) synapses received by cortical pyramidal neurons (PNs). SRGAP2C binds to and inhibits all known functions of SRGAP2A leading to an increase in E and I synapse density and protracted synapse maturation, traits characterizing human cortical neurons. Here, we demonstrate how the evolutionary changes that led to the emergence of SRGAP2 HSGDs generated

SUBMITTER: Schmidt ERE 

PROVIDER: S-EPMC6904453 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature