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Publications in Cognitive function by NOMIS researchers

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NOMIS Researcher(s)

Published in

October 14, 2024

Human-specific (HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear. Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic gene SRGAP2A, in human cortical pyramidal neurons (CPNs) xenotransplanted in the mouse cortex. Downregulation of SRGAP2B/C in human CPNs led to strongly accelerated synaptic development, indicating their requirement for the neoteny that distinguishes human synaptogenesis. SRGAP2B/C genes promoted neoteny by reducing the synaptic levels of SRGAP2A,thereby increasing the postsynaptic accumulation of the SYNGAP1 protein, encoded by a major intellectual disability/autism spectrum disorder (ID/ASD) gene. Combinatorial loss-of-function experiments in vivo revealed that the tempo of synaptogenesis is set by the reciprocal antagonism between SRGAP2A and SYNGAP1, which in human CPNs is tipped toward neoteny by SRGAP2B/C. Thus, HS genes can modify the phenotypic expression of genetic mutations leading to ID/ASD through the regulation of human synaptic neoteny.

Research field(s)
Genetics & Heredity

NOMIS Researcher(s)

October 1, 2024

Animal speciation often involves novel behavioral features that rely on nervous system evolution. Human-specific brain features have been proposed to underlie specialized cognitive functions and to be linked, at least in part, to the evolution of synapses, neurons, and circuits of the cerebral cortex. Here, we review recent results showing that, while the human cortex is composed of a repertoire of cells that appears to be largely similar to the one found in other mammals, human cortical neurons do display specialized features at many levels, from gene expression to intrinsic physiological properties. The molecular mechanisms underlying human species-specific neuronal features remain largely unknown but implicate hominid-specific gene duplicates that encode novel molecular modifiers of neuronal function. The identification of human-specific genetic modifiers of neuronal function brings novel insights on brain evolution and function and, could also provide new insights on human species-specific vulnerabilities to brain disorders.

Research field(s)
Genetics & Heredity, Evolutionary Biology