The left and right distribution of a set of twenty‐six genes in the zebrafish pallium was examined by RT‐qPCR experiments. The analysis comprised four general pallial markers (eomesa, emx2, emx3 and prox1); eight genes, dapper1, htr3a, htr3b, htr4, id2, ndr2, pkcβ and lmo4, that have been described as asymmetric distributed in the brain of mammals (human and mouse); six genes, arrb2, auts2, baiap2, fez1, gap43 and robo1, asymmetrically distributed in the mammalian cortex, that have been associated with autism in humans; and, eight genes, baz1b, fzd9, limk1, tubgcp5, cyfip1, grik1a, nipa1 and nipa2, which have been associated with developmental dyscalculia, a brain disability linked to brain laterality in humans. We found a leftward bias in the expression of 10 genes (dapper1, htr3a, htr3b, htr4, id2, ndr2, pkcß, auts2, baiap2 and grik1a) and a rightward bias for 5 genes (lmo4, arrb2, fez1, gap43, robo1) in agreement with the data reported in mammals. We also found a rightward lateralization for nipa1 and nipa2, whereas the remaining genes (eomesa, emx2, emx3, prox1, baz1b, cyfip1, fzd9, limk1 and tubgpc5) were bilaterally distributed. These findings suggest a basic homology in the asymmetric expression of several pallial vertebrate genes.

Autism spectrum disorders (ASDs) comprise a genetically heterogeneous group of conditions characterized by a multifaceted range of impairments and multifactorial etiology. Epidemiological studies have identified valproic acid (VPA), an anticonvulsant used to treat epilepsy, as an environmental factor for ASDs. Based on these observations, studies using embryonic exposure to VPA have been conducted in many vertebrate species to model ASD. The zebrafish is emerging as a popular model in biomedical research to study the molecular pathways involved in nervous system disorders. VPA exposure in zebrafish larvae has been shown to produce a plethora of effects on social, motor and anxiety behavior, and several genetic pathways altered by VPA have been described. However, the doses and regimen of administration reported in the literature are very heterogenous, creating contradictory results and posing serious limits to the interpretation of VPA action on neurodevelopment. To shed light on the toxic effect of VPA, we tested micromolar concentrations of VPA, using exposure for 24 and 48 h in two different zebrafish strains. Our results show that micromolar doses of VPA mildly affect embryo survival but are sufficient to induce molecular alterations in neurodevelopmental genes previously shown to be influenced by VPA, with substantial differences between strains.

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