Taking some time to enjoy the
#Oktoberfest with the team! A great chance to unwind and celebrate together. Prost to good company, and great teamwork! 🍻
#LabLife #NewsMayerlabEnhancers that drive projection neuron-specific gene expression are accessible in all parts of the GE (ATAC-seq Rhodes et al). Yet, their activity is restricted to the LGE. Thus, "differential TF binding" rather than "differential accessibility" induces projection neuron fate 6/7
We conducted ChIP-seq and luciferase reporter assays and found that MEIS2 requires the presence of DLX to direct its functional activity towards regulatory elements of projection neuron genes containing specific DLX/MEIS co-binding sites. 5/7
By combining tCROPseq CRISPR perturbation sequencing and barcode lineage tracing (TrackerSeq) in vivo, we provide further evidence that MEIS2 perturbation results in a fate switch from LGE projection neurons to interneurons. 4/7
We developed a transposon-based version of CROP-seq (tCROP-seq) with improved in vivo efficiency. Its application confirmed our hypothesis: MEIS2 removal decreased the proportion of projection neurons and increased the proportion of interneurons, suggesting a fate switch. 3/7
In Bandler et al. we showed that in the GE single cell trajectories of projection and interneurons diverge from a common pool of mitotic progenitors (
https://doi.org/10.1016/j.conb.2023.102691). We now show that MEIS2 expression is the strongest predictor of projection neuron fate. 2/7
After many years, it's great to be back in Milano! I'm here to attend the EMBO YIN Meeting at IFOM - looking forward to day 2 of a great event!
#EMBOYIN #IFOM #NewsMayerlabExcited to share our new study combining in vivo CRISPR perturbation sequencing with barcode-based lineage tracing. The study reveals a mechanism by which selective enhancer activation establishes the identity of GABAergic projection neurons. Our work may help to understand the mechanism of disease associated with Meis2 mutations.
https://www.biorxiv.org/content/10.1101/2023.01.30.525356v1#neuroscience #devbio #devbiol #Genomics #NGS #Genetics #science #neuro #neurodevelopment #NewsMayerlab