bProneural NEUROG2 (neurogenin 2 [Ngn2]) is essential for neuronal commitment, cell cycle withdrawal, and neuronal differentiation. Although NEUROG2's influence on neuronal commitment and differentiation is beginning to be clarified, its role in cell cycle withdrawal remains unknown. We therefore set out to investigate the molecular mechanisms by which NEUROG2 induces cell cycle arrest during spinal neurogenesis. We developed a large-scale chicken embryo strategy, designed to find gene networks modified at the onset of NEUROG2 expression, and thereby we identified those involved in controlling the cell cycle. NEUROG2 activation leads to a rapid decrease of a subset of cell cycle regulators acting at G 1 and S phases, including CCND1, CCNE1/2, and CCNA2 but not CCND2. The use of NEUROG2VP16 and NEUROG2EnR, acting as the constitutive activator and repressor, respectively, indicates that NEUROG2 indirectly represses CCND1 and CCNE2 but opens the possibility that CCNE2 is also repressed by a direct mechanism. We demonstrated by phenotypic analysis that this rapid repression of cyclins prevents S phase entry of neuronal precursors, thus favoring cell cycle exit. We also showed that cell cycle exit can be uncoupled from neuronal differentiation and that during normal development NEUROG2 is in charge of tightly coordinating these two processes.O ne important challenge in neurobiology is to understand how different types of postmitotic neurons, with distinct cellular and physiological properties, are generated in the developing central nervous system (CNS) from a pool of dividing neural progenitors. The embryonic spinal cord is a good model to tackle these issues, because the role of extracellular signals and transcription factors in neuron specification and differentiation is relatively well defined. This structure is derived from the neural tube, a single pseudoepithelium that will sequentially give rise to a large variety of neurons and glial cells dedicated to serve specific functions in the adult. Neurogenesis is achieved via a succession of steps that follow a stereotypic temporal order. A neural progenitor is committed to a neuronal fate at the expense of a glial fate and becomes a neuronal precursor. Concomitantly, this neural progenitor is destined to differentiate into a specific neuronal subtype. Soon after, neuronal precursors stop cycling and initiate their differentiation to give rise to postmitotic differentiated neurons.The main positive regulators of vertebrate neurogenesis are proneural transcription factors of the neural basic helix-loop-helix (bHLH) family, including neurogenins (NeuroG1/2/3) (5, 35). They control different steps of neurogenesis, such as neuronal commitment, cell cycle exit, subtype specification, and neuronal differentiation (5, 35, 42). In the spinal cord, loss-of-function studies have shown that NEUROG2 is involved in the acquisition of motoneuron and interneuron fates (46). Together with NEUROG1, NEUROG2 also controls neuronal differentiation as shown by the loss of neurons in Ne...