Dysregulation of astrocyte extracellular signaling in Costello syndrome

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Science Translational Medicine  06 May 2015:
Vol. 7, Issue 286, pp. 286ra66
DOI: 10.1126/scitranslmed.aaa5645

Perineuronal nets close the door on brain development

Creating a brain is exceedingly complex, so mutations in many different genes can cause the process to go awry. Mutations in one sensitive pathway, Ras signaling, cause a family of neurodevelopmental disorders called RASopathies. Krencik et al. have used patient-derived iPSCs and mutant mice to demonstrate that the mutation in HRAS that causes one RASopathy—Costello syndrome—acts by accelerating astrocyte differentiation. The authors examined astroglial development from patient iPSCs in vitro and, similarly, astroglial development in vivo in mice carrying the same mutation as that found in Costello syndrome patients. The authors suggest that premature formation of perineuronal nets around neurons may close the experience-dependent development of the brain, producing the typical intellectual disability in Costello syndrome patients.

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