Conditional Loss of BAF (mSWI/SNF) Scaffolding Subunits Affects Specification and Proliferation of Oligodendrocyte Precursors in Developing Mouse Forebrain

Oligodendrocytes are responsible for axon myelination in the brain and spinal cord. Generation of oligodendrocytes entails highly regulated multistage neurodevelopmental events, including proliferation, differentiation and maturation. The chromatin remodeling BAF (mSWI/SNF) complex is a notable regulator of neural development. In our previous studies, we determined the indispensability of the BAF complex scaffolding subunits BAF155 and BAF170 for neurogenesis, whereas their role in gliogenesis is unknown. Here, we show that the expression of BAF155 and BAF170 is essential for the genesis of oligodendrocytes during brain development. We report that the ablation of BAF155 and BAF170 in the dorsal telencephalic (dTel) neural progenitors or in oligodendrocyte-producing progenitors in the ventral telencephalon (vTel) in double-conditional knockout (dcKO) mouse mutants, perturbed the process of oligodendrogenesis. Molecular marker and cell cycle analyses revealed impairment of oligodendrocyte precursor specification and proliferation, as well as overt depletion of oligodendrocytes pool in dcKO mutants. Our findings unveil a central role of BAF155 and BAF170 in oligodendrogenesis, and thus substantiate the involvement of the BAF complex in the production of oligodendrocytes in the forebrain.

Temporally Distinct Roles for the Zinc Finger Transcription Factor Sp8 in the Generation and Migration of Dorsal Lateral Ganglionic Eminence (dLGE)-Derived Neuronal Subtypes in the Mouse

Progenitors in the dorsal lateral ganglionic eminence (dLGE) are known to give rise to olfactory bulb (OB) interneurons and intercalated cells (ITCs) of the amygdala. The dLGE enriched transcription factor Sp8 is required for the normal generation of ITCs as well as OB interneurons, particularly the calretinin (CR)-expressing subtype. In this study, we used a genetic gain-of-function approach in mice to examine the roles Sp8 plays in controlling the development of dLGE-derived neuronal subtypes. Misexpression of Sp8 throughout the ventral telencephalic subventricular zone (SVZ) from early embryonic stages, led to an increased generation of ITCs which was dependent on Tshz1 gene dosage. Additionally, Sp8 misexpression impaired rostral migration of OB interneurons with clusters of CR interneurons seen in the SVZ along with decreased differentiation of calbindin OB interneurons. Sp8 misexpression throughout the ventral telencephalon also reduced ventral LGE neuronal subtypes including striatal projection neurons. Delaying Sp8 misexpression until E14–15 rescued the striatal and amygdala phenotypes but only partially rescued OB interneuron reductions, consistent with an early window of striatal and amygdala neurogenesis and ongoing OB interneuron generation at this late stage. Our results demonstrate critical roles for the timing and neuronal cell-type specificity of Sp8 expression in mouse LGE neurogenesis.

The Polycomb group protein Ring1 regulates dorsoventral patterning of the mouse telencephalon

Dorsal-ventral patterning of the mammalian telencephalon is fundamental to the formation of distinct functional regions including the neocortex and ganglionic eminence. While Bone morphogenetic protein (BMP), Wnt, and Sonic hedgehog (Shh) signaling are known to determine regional identity along the dorsoventral axis, how the region-specific expression of these morphogens is established remains unclear. Here we show that the Polycomb group (PcG) protein Ring1 contributes to the ventralization of the mouse telencephalon. Deletion of Ring1b or both Ring1a and Ring1b in neuroepithelial cells induces ectopic expression of dorsal genes, including those for BMP and Wnt ligands, as well as attenuated expression of the gene for Shh, a key morphogen for ventralization, in the ventral telencephalon. We observe PcG protein–mediated trimethylation of histone 3 at lysine-27 and binding of Ring1B at BMP and Wnt ligand genes specifically in the ventral region. Furthermore, forced activation of BMP or Wnt signaling represses Shh expression. Our results thus indicate that PcG proteins suppress BMP and Wnt signaling in a region-specific manner and thereby allow proper Shh expression and development of the ventral telencephalon.

Gene expression correlates of social evolution in coral reef butterflyfishes

Animals display remarkable variation in social behaviour. However, outside of rodents, little is known about the neural mechanisms of social variation, and whether they are shared across species and sexes, limiting our understanding of how sociality evolves. Using coral reef butterflyfishes, we examined gene expression correlates of social variation (i.e. pair bonding versus solitary living) within and between species and sexes. In several brain regions, we quantified gene expression of receptors important for social variation in mammals: oxytocin ( OTR ), arginine vasopressin ( V1aR ), dopamine ( D1R, D2R ) and mu-opioid ( MOR ). We found that social variation across individuals of the oval butterflyfish, Chaetodon lunulatus, is linked to differences in OTR , V1aR, D1R, D2R and MOR gene expression within several forebrain regions in a sexually dimorphic manner. However, this contrasted with social variation among six species representing a single evolutionary transition from pair-bonded to solitary living. Here, OTR expression within the supracommissural part of the ventral telencephalon was higher in pair-bonded than solitary species, specifically in males. These results contribute to the emerging idea that nonapeptide, dopamine and opioid signalling is a central theme to the evolution of sociality across individuals, although the precise mechanism may be flexible across sexes and species.