Ptf1a promotes an inhibitory peptidergic identity in cortical pyramidal cells in vivo. Mus musculus

Ptf1a has been shown to be necessary for determining an inhibitory interneuronal fate in many regions of the nervous system. In this study, we aim to investigate the sufficiency of Ptf1a to cell-autonomously promote a specific neuronal identity by misexpressing it in developing excitatory cortical pyramidal cells and studying its impact on pyramidal cell features, such as its gene expression profile. To accomplish this, we electroporate either a Ptf1a/GFP-misexpression construct or a GFP-only control construct into E12.5 mouse embryonic cortices, harvest the cortices at E15.5, and examine Ptf1a-induced changes to the pyramidal cell transcriptome, molecular expression pattern, neurotransmitter status, and morphology. We conclude that Ptf1a is sufficient to cell-autonomously promote an inhibitory peptidergic identity and alter neuronal morphology in developing cortical pyramidal cells. The results of this study provide insight into intrinsic transcriptional controls over neuronal identity, specifically implicate Ptf1a as a potent regulator of an inhibitory peptidergic identity, and may guide future studies of neuronal reprogramming for circuit repair after disease or injury. Overall design: Purified GFP-expressing cells were isolated from mouse embryonic cortices electroporated with either a Ptf1a/GFP-misexpressing construct or a GFP-only control construct. 3-6 brains were collected per sample, yielding 58-106,000 cells per sample. Ptf1a/GFP-misexpressing samples were run in triplicate, GFP-only control samples were run in duplicate.