Ptbp1 is not required for retinal neurogenesis and cell fate specification [RNA-seq]

The RNA-binding protein Ptbp1 has been proposed as a master regulator of neuronal fate, repressing neurogenesis through its effects on alternative splicing and miRNA maturation. While prior studies using RNA interference suggested that Ptbp1 loss promotes neurogenesis, recent genetic studies have failed to replicate glia-to-neuron conversion following Ptbp1 loss of function. To evaluate the role of Ptbp1 in developmental neurogenesis in vivo, we conditionally disrupted Ptbp1 in retinal progenitors. Ptbp1 was robustly expressed in both retinal progenitors and Müller glia but absent from postmitotic neurons, and efficient loss of function in mutant animals was confirmed using immunostaining for Ptbp1. Furthermore, bulk RNA-Seq at E16 revealed accelerated expression of late-stage progenitor and photoreceptor-specific genes and altered splicing patterns in Ptbp1 mutants, including increased inclusion of neuron- and retina-specific exons. However, we observed no defects in retinal lamination, progenitor proliferation, or cell fate specification in mature retina. ScRNA-Seq of mature mutant retinas revealed only modest transcriptional changes limited to Müller glia, recapitulating alterations seen following selective deletion of Ptbp1 in mature glia. Our findings demonstrate that Ptbp1 is fully dispensable for retinal development and suggest that its proposed role as a central repressor of neurogenesis should be reevaluated Bulk RNA-seq was performed on Chx10Cre control (WT) , Chx10Cre;Ptbp1lox/WT (HET), and Chx10Cre;Ptbp1lox/lox (KO) retinas at E16 and sequenced on the Illumina NovaSeq X platform