John Rubenstein and colleagues identified WNT signaling as a key mediator of Tbr1-dependent functions in deep-layer cortical neurons, and showed that normalizing WNT signaling rescues particular mutant phenotypes.
Research Highlights
Highlights of SFARI-funded papers, selected by the SFARI science team.
Kurt Haas and colleagues used multiple models and bioassays to assess the functional impact of more than 100 missense and nonsense mutations in PTEN, allowing for high-confidence predictions of pathogenicity.
Molecular mechanisms of fragile X syndrome
Kimberly Huber, Joel Richter and colleagues showed that FMRP deficiency in mice leads to changes in a key histone modification across the genome, with subsequent effects on alternative splicing of many ASD risk genes.
Microexon splicing and translation in ASD
Benjamin Blencowe and colleagues defined the functional roles of microexons in genes encoding translation initiation factors, linking them to altered translation, synaptic plasticity and behavior.
First 1,000 participants in RI-CART study
Eric Morrow, Stephen Sheinkopf and colleagues reported the characteristics of the first 1,000 participants in the RI-CART study, a population-based cohort of individuals with autism in Rhode Island.
Foxp1 and the striatum
Genevieve Konopka and colleagues reported important roles for Foxp1 in particular subclasses of the spiny projection neurons in the striatum, with downstream effects on striatal-dependent circuits and behaviors.
Paraventricular oxytocin neurons support social behavior
Garret Stuber and colleagues used in vivo calcium imaging to show that a population of oxytocin-positive (OT) neurons in the paraventricular nucleus of the hypothalamus responds preferentially to social stimuli and is necessary for regulating social behavior. Reduced number of OT neurons was associated with social deficits in Shank3b KO mice.
USP9X mutation defines a neurodevelopmental syndrome
Michael Piper and colleagues confirmed and extended the association of USP9X loss-of-function mutations with a neurodevelopmental syndrome in both sexes, driven by changes in multiple signaling pathways.
Exome sequencing identifies new ASD risk genes
Joseph Buxbaum and colleagues in the Autism Sequencing Consortium reported the largest exome sequencing study of ASD to date, identifying 102 risk genes at a false discovery rate of 0.1 or less.
Shank3 is necessary for homeostatic plasticity
Gina Turrigiano and colleagues showed that loss of Shank3 disrupts homeostatic plasticity and that this deficit can be rescued by the mood-stabilizing drug lithium (Li+).