The Journal of Neuroscience, May 6, 2015 • 35(18):i • i

This Week in The Journal

Motion Integration Is Enhanced in grate information from many dots. The , encodes a component of the exon Autism authors thus conclude that deficits in co- junction complex (EJC). This com- herent motion tasks arise because people plex, which attaches to mRNA sites where two exons are joined during splicing, facili- Catherine Manning, Marc S. Tibber, with autism do not effectively discount in- tates nuclear export and promotes assembly Tony Charman, Steven C. Dakin, and formation from randomly moving dots. of translation machinery on mRNAs. Be- Elizabeth Pellicano One can imagine that a failure to ig- nore irrelevant information could under- cause EJCs are removed during the first (see pages 6979–6986) lie some of the behavioral manifestations round of translation, they selectively en- hance translation of newly synthesized Autism is a neurodevelopmental disorder of autism, such as a failure to preferen- tially attend to faces and hypersensitivity mRNAs. Thus, EJCs can speed the produc- defined by impaired social interactions tion of in response to extracellular to lights and sounds. However, defini- and an unusually narrow scope of inter- signals. In addition, the EJC helps prevent tively linking the neural bases of percep- ests. In addition to high-level behavioral the production of truncated proteins by sig- and cognitive symptoms, low-level sen- tual and behavioral deficits in autism will naling the presence of a premature stop sory processing is altered in autism. In require much more work. codon: if an mRNA contains a stop codon some tasks, people with autism have en- upstream of a splice junction, the presence hanced perceptual abilities. For example, of an EJC at that junction triggers a decay they are unusually adept at visual tasks process that eliminates the transcript. that require attending to fine detail and In forming EJCs, Rbm8a heterodi- ignoring context, such as finding hidden merizes with another protein, Magoh. shapes in a drawing. Conversely, people Because previous studies reported that hap- with autism are impaired on tasks requir- loinsufficiency of Magoh causes microceph- ing integration of motion information. aly in mice, Mao et al. reasoned that loss of For example, when presented with a field Rbm8a may underlie microcephaly in of dots in which some move in the same 1q21.1 deletion syndromes. Indeed, delet- direction while the remainder move in ing one copy of Rbm8a in mouse neural random directions, people with autism progenitors starting at embryonic day 9.5 require a greater proportion of coherently moving dots to accurately report the decreased Rbm8a protein levels by 70% and movement direction. caused cortical thinning. This thinning ap- Three hypotheses have been proposed peared to stem from premature exit of radial to explain increased coherent motion glia cells from the cell cycle, resulting in ex- thresholds in autism. First, the deficit may cess neuron production at a stage when cell result from inaccuracy in estimating the divisions should have been expanding the direction of individual dots. Alternatively, progenitor pool. Consistent with this hy- it could reflect impaired integration of pothesis, more than twice as many neurons motion information gathered from differ- were present in Rbm8a-haploinsufficient ent points in the visual field. Finally, it neocortex than in controls. Many excess may stem from difficulty in ignoring the neurons were subsequently eliminated by apoptosis, and the vast majority of neurons irrelevant dots. To test these alternatives, Mice happloinsufficient for Rbm8a (bottom) had fewer radial Manning et al. used a motion-detection glia cells (green) in the developing neocortex at embryonic present at birth expressed markers of early- task in which all dots contained signal: the day12.5thancontrolbrains(top).SeethearticlebyMaoetal. born, lower-layer neurons; few later-born, movement directions were normally dis- for details. upper-layer neurons were present. tributed around a mean, and participants These results support the hypothesis were asked to discern the mean move- Loss of Exon Junction Complex that Rbm8a haploinsufficiency contrib- utes to phenotypes observed in 1q21.1 de- ment direction. When all dots were mov- Protein Causes Microcephaly ing in the same direction (i.e., there was letion syndromes. Although Rbm8a has some EJC-independent functions, given no variability), children with autism were Hanqian Mao, Louis-Jan Pilaz, John J. that the effects of Rbm8a haploinsuffi- able to discern motion direction as accu- McMahon, Christelle Golzio, Danwei Wu, et al. rately as controls, arguing against the first ciency were similar to those reported for hypothesis. Unexpectedly, when the di- (see pages 7003–7018) Magoh haploinsufficiency (Silver et al., 2010, Nat Neurosci 13:551), it is likely that rection variability was high, those with au- Deletions of portions of the 1q21.1 locus on loss of EJC function caused the premature tism were more accurate than controls in human 1 result in various generation of neurons and their subse- discerning the mean direction. This sug- phenotypes, which may include intellectual quent loss by apoptosis. gests, contrary to the second hypothesis, disability, schizophrenia, and microcephaly. that autism enhances the ability to inte- Rbm8a, one of several present at this This Week in The Journal is written by X Teresa Esch, Ph.D.