SYNGAP1 deficiency disrupts neoteny in human cortical neurons in vivo.
Vermaercke, B.; Iwata, R.; Wierda, K.; Boubakar, L.; Rodriguez, P.; Ditkowska, M.; Bonin, V. V.; Vanderhaeghen, P.
Show abstract
Intellectual deficiency (ID) and autism spectrum disorder (ASD) originate from disrupted development of human-specific cognitive functions. Human brain ontogeny is characterized by a considerably prolonged, neotenic, cortical neuron development. Neuronal neoteny could be disrupted in ID/ASD, but this was never tested because of the difficulties to study developing human cortical circuits. Here we use xenotransplantation of human cortical neurons into the mouse cortex to study the in vivo neuronal consequences of SYNGAP1 haploinsufficiency, a frequent cause of ID/ASD. We find that SYNGAP1 deficient neurons display strong acceleration of morphological and functional synaptic development. At the circuit level, SYNGAP1 haploinsufficient neurons display disrupted neoteny, with faster integration into cortical circuits and acquisition of sensory responsiveness months ahead of time. These data link neuronal neoteny to ID/ASD, with important implications for diagnosis and treatments.
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