Neurogenesis is a key developmental event through which neurons are generated from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes have been reported to play essential roles in the neurogenesis of the central nervous system. However, whether BAF complexes are required for neuron generation in the olfactory system is unknown. Here, we identified onscBAF and ornBAF complexes, which are specifically present in olfactory neural stem cells (oNSCs) and olfactory receptor neurons (ORNs), respectively. We demonstrated that BAF155 subunit is highly expressed in both oNSCs and ORNs, whereas high expression of BAF170 subunit is observed only in ORNs. We report that conditional deletion of BAF155, a core subunit in both onscBAF and ornBAF complexes, causes impaired proliferation of oNSCs as well as defective maturation and axonogenesis of ORNs in the developing olfactory epithelium (OE), while the high expression of BAF170 is important for maturation of ORNs. Interestingly, in the absence of BAF complexes in BAF155/BAF170 double-conditional knockout mice (dcKO), OE is not specified. Mechanistically, BAF complex is required for normal activation of Pax6-dependent transcriptional activity in stem cells/progenitors of the OE. Our findings unveil a novel mechanism mediated by the mSWI/SNF complex in OE neurogenesis and development.

Modeling the complicated chemical reactions in the interstellar medium and surface materials of Titan is nontrivial. Since both the atmosphere and the surface are rich in organic molecules, the chemistry may have important implications for the origin of biomolecules. Prebiotic synthesis of DNA nucleobases from simple molecules such as formamide has been known for more than half a century. In this study, new free radical pathways leading to the synthesis of guanine, hypoxanthine, purine, and adenine have been studied using density functional theory (B3LYP with the 6-311G(d,p) basis set). The pathways of the selected nucleobases demonstrate the importance of free radicals in the production of useful biomolecules under conditions appropriate for the interstellar medium or on Titan. The pathways may be universal in nature and proceed without solvent requirements. Calculations indicate that radical pathways yield lower reaction barriers as compared to previously reported pathways. Overall, these results suggest that the chemistry on Titan's surface and/or the growth of organic particulates in the haze layers in Titan's atmosphere likely involve free radicals. The mechanisms demonstrate that important prebiotic precursors can be predicted. The reaction sequences reported here may lead to the production and build-up of molecules with prebiotic relevance.

SummaryDuring early cortical development, neural stem cells (NSCs) divide symmetrically to expand the progenitor pool, whereas, in later stages, NSCs divide asymmetrically to self-renew and produce other cell types. The timely switch from such proliferative to differentiative division critically determines progenitor and neuron numbers. However, the mechanisms that limit proliferative division in late cortical development are not fully understood. Here, we show that the BAF (mSWI/SNF) complexes restrict proliferative competence and promote neuronal differentiation in late corticogenesis. Inactivation of BAF complexes leads to H3K27me3-linked silencing of neuronal differentiation-related genes, with concurrent H3K4me2-mediated activation of proliferation-associated genes via de-repression of Wnt signaling. Notably, the deletion of BAF complexes increased proliferation of neuroepithelial cell-like NSCs, impaired neuronal differentiation, and exerted a Wnt-dependent effect on neocortical and hippocampal development. Thus, these results demonstrate that BAF complexes act as both activators and repressors to control global epigenetic and gene expression programs in late corticogenesis.

Engineering of metabolic pathways by genetic modification has been restricted largely to enzyme-encoding structural genes. The product yield of such pathways is a quantitative genetic trait. Out of 52 Saccharomyces cerevisiae strains phenotyped in small-scale fermentations, we identified strain CBS6412 as having unusually low glycerol production and higher ethanol yield as compared to an industrial reference strain. We mapped the QTLs underlying this quantitative trait with pooled-segregant whole-genome sequencing using 20 superior segregants selected from a total of 257. Plots of SNP variant frequency against SNP chromosomal position revealed one major and one minor locus. Downscaling of the major locus and reciprocal hemizygosity analysis identified an allele of SSK1, ssk1(E330N…K356N), expressing a truncated and partially mistranslated protein, as causative gene. The diploid CBS6412 parent was homozygous for ssk1(E330N…K356N). This allele affected growth and volumetric productivity less than the gene deletion. Introduction of the ssk1(E330N…K356N) allele in the industrial reference strain resulted in stronger reduction of the glycerol/ethanol ratio compared to SSK1 deletion and also compromised volumetric productivity and osmotolerance less. Our results show that polygenic analysis of yeast biodiversity can provide superior novel gene tools for metabolic engineering.

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