Hitherto, the known mechanisms underpinning cell-fate specifcation act on neural progenitors, afecting their commitment to generate neuron or glial cells. Here, we show that particular phospholipids supplemented in the culture media modify the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine (PtdCho)-enriched media enhances neuronal diferentiation at the expense of astroglial and unspecifed cells. Conversely, phosphatidylethanolamine (PtdEtn) enhances astroglial diferentiation and accelerates astrocyte maturation. The ability of phospholipids to modify the fate of post-mitotic cells depends on its presence during a narrow time-window during cell diferentiation and it is mediated by the selective activation of particular signaling pathways. While PtdCho-mediated efect on neuronal diferentiation depends on cAMP-dependent kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates astrogliogenesis through the activation of the MEK/ ERK signaling pathway. Collectively, our results provide an additional degree of plasticity in neural cell specifcation and further support the notion that cell diferentiation is a reversible phenomenon. They also contribute to our understanding of neuronal and glial lineage specifcation in the central nervous system, opening up new avenues to retrieve neurogenic capacity in the brain.Author correction: The original version of this Article contained a typographical error in the spelling of the author Marcelo Einicker-Lamas, which was incorrectly given as Marcelo Einiker-Lamas. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file.Fil: Montaner, Aneley Natalia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.Fil: Da Silva Santana, Themis Taynah. University of Rio Grande do Norte. Brain Institute; Brazil.Fil: Schroeder, Timm. Swiss Federal Institute of Technology in Zurich (ETH). Department of Biosystems Science and Engineering. Research Group Cell Systems Dynamics; Switzerland.Fil: Einicker-Lamas, Marcelo. Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho; Brasil.Fil: Girardini, Javier. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.Fil: Costa, Marcos Romualdo. University of Rio Grande do Norte. Brain Institute; Brazil.Fil: Banchio, Claudia. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario (IBR -CONICET); Argentina.