SUMMARY Fragile X syndrome (FXS), the leading monogenic cause of intellectual disability and autism, results from loss of function of the RNA-binding protein FMRP. Here we show that FMRP regulates the translation of neuronal nitric oxide synthase 1 (NOS1) in the developing human neocortex. Whereas NOS1 mRNA is ubiquitously expressed, NOS1 protein is transiently co-expressed with FMRP during early synaptogenesis in layer- and region-specific subpopulations of pyramidal neurons. These include mid-fetal layer 5 subcortically projecting neurons arranged into alternating columns in the prospective Broca’s area and orofacial motor cortex. Human NOS1 translation is activated by FMRP via interactions with coding region binding motifs absent from mouse Nos1 mRNA, which is expressed in mouse pyramidal neurons, but not efficiently translated. Correspondingly, neocortical NOS1 protein levels are severely reduced in developing human FXS cases but not FMRP-deficient mice. Thus, alterations in FMRP post-transcriptional regulation of NOS1 in developing neocortical circuits may contribute to cognitive dysfunction in FXS.

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Cellular reagents could be prepared for polymerase to lower the cost of reagents for PCR-based workshops delivered as outreach out of community labs. Research in the methods for accomplishing such a feat would contribute to global efforts to better document the process of making enzymes used as biotech reagents at the small-scale. Furthermore, well-documented protocols would provide an opportunity for volunteers to participate in preparing the materials for PCR & Pizza. Ultimately this would serve to develop and highlight the capacity to create low-cost enzyme reagents within community labs.

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