How to make neurons--thoughts on the molecular logic of neurogenesis in the central nervous system

Neuronal differentiation relies on a set of interconnected molecular events to achieve the differentiation of pan-neuronal hallmarks, together with neuronal subtype-specific features. Here, we propose a conceptual framework for these events, based on recent findings. This framework encompasses a dimension in time during development, progressing from early master regulators to later expressed effector genes and terminal selector genes. As a horizontal intersection, we propose the action of permissive fate determinants that are critical in allowing progression through the above transcriptional phases. Typically, these are widely expressed and often interact with the chromatin remodeling machinery. We conclude by discussing this model in the context of the direct fate conversion of various somatic cells into neurons.