Identification of FMRP target genes expressed in corticogenesis: implication for common phenotypes among neurodevelopmental disorders

Abstract

Keywords: FMRP, FXS, mRNA targets, corticogenesis al., 2014). Postnatally, FMRP is localized in the cell body, proximal dendrites and axons of neurons (Darnell et al., 2011;Castrén, 2016), and plays profound regulatory roles in the synaptic function and neuronal plasticity (Bassell and Warren, 2008; De Rubeis and Bagni, 2010) through interaction with transcripts that encode pre-and postsynaptic proteins, and also regulation of mRNA trafficking into dendrites (Abrahams and Geschwind, 2008;Bassell and Warren, 2008;Abrahams et al., 2013).Altogether, FMRP has multifunctional roles at distinct times in brain development.Since the discovery of FMRP, a large effort has been made to characterize targets of FMRP using several methods including RNA immunoprecipitation (RIP) Protein-protein association networkTo predict biological functions, pathways, and protein-protein interactions, 124 proteins encoded by both FMRP targets and ASD-associated genes were analyzed using the STRING Database (Szklarczyk et al., 2017). Four statistically significant functional clusters were selected and highlighted (FDR<0.05; Figure 3). The cluster with the largest number of FMRP targets/ASD-associated genes was categorized as "transcription regulation" comprised of 28 genes, i.e.,