Decreased expression of axon-guidance receptors in the anterior cingulate cortex in autism

Abstract

BackgroundAxon-guidance proteins play a crucial role in brain development. As the dysfunction of axon-guidance signaling is thought to underlie the microstructural abnormalities of the brain in people with autism, we examined the postmortem brains of people with autism to identify any changes in the expression of axon-guidance proteins.ResultsThe mRNA and protein expression of axon-guidance proteins, including ephrin (EFN)A4, eEFNB3, plexin (PLXN)A4, roundabout 2 (ROBO)2 and ROBO3, were examined in the anterior cingulate cortex and primary motor cortex of autistic brains (n = 8 and n = 7, respectively) and control brains (n = 13 and n = 8, respectively) using real-time reverse-transcriptase PCR (RT-PCR) and western blotting. Real-time RT-PCR revealed that the relative expression levels of EFNB3, PLXNA4A and ROBO2 were significantly lower in the autistic group than in the control group. The protein levels of these three genes were further analyzed by western blotting, which showed that the immunoreactive values for PLXNA4 and ROBO2, but not for EFNB3, were significantly reduced in the ACC of the autistic brains compared with control brains.ConclusionsIn this study, we found decreased expression of axon-guidance proteins such as PLXNA4 and ROBO2 in the brains of people with autism, and suggest that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism.

Detecting ancient positive selection in humans using extended lineage sorting

“…SLITs proteins act as attractive or repulsive signals for axons expressing different ROBO receptors. ROBO2 has been further associated with vocabulary growth (St Pourcain et al 2014), autism (Suda et al 2011), and dyslexia (Fisher and DeFries 2002) and is involved in the development of neural circuits related to vocal learning in birds (Wang et al 2015). Interestingly, ROBO2 is also in a long desert of both Denisovan and Neandertal ancestry in non-Africans.…”

A Genome Wide Copy Number Variations Analysis in Autism Spectrum Disorder (Asd) and Intellectual Disability (Id) in Italian Families

“…A 1.05 Mb de novo gain involving PLXNA4 was identified in an ASD case. Decreased expression of axon-guidance proteins, as PLXNA4, was found in the brains of people with ASD, suggesting that dysfunctional axon-guidance protein expression may play an important role in the pathophysiology of autism [9]. Handrigan data highlight 16q24.2 as a region of interest for ASD, ID and congenital renal malformations.…”

“…We identified the following rearrangements: a duplication of NPHP1 gene in 2q13 [8]; a de novo 7q32.3 gain involving PLXNA4 [9]; a 9p24.3 duplication involving KANK1 gene [10]; a duplication of PTCH1 in 9q22 [11]; a 5.8 Mb deletion on 12p12.2p12.1 including SOX5 [12]; a duplication of the 16q24.2 region [13]; an inherited 20p12.1 deletion interrupting the MACROD2 gene [14]; a Xp11.22 duplication involving KDM5C and IQSEC2 [15]; a duplication in Xp22.12 including the RPS6KA3 gene [16]; and the deletion of PTCHD1 in Xp22.11 [17]. …”

Role ofp53, Mitochondrial DNA Deletions, and Paternal Age in Autism: A Case-Control Study

“…[9][10][11][12] Studies have linked p53 to developmental abnormalities 13 (see also Supplemental Table 5), and regions adjacent to 17p13.1 encoding for proteins with important roles in brain function and neurodevelopment (eg, axonal dynein heavy chain 2 and Na + /K + ATPase subunit β-2) and others have been found to be associated with autism (AU) (eg, ephrin-B3 14 ). Increased p53/Bcl2 protein ratios had been found in brain regions of a small set of autistic subjects [15][16][17] ; however, no characterization of posttranslational modifications or functional status of p53 was undertaken.…”