Figure 3. Model of spatiotemporal regulation of differential neurogenesis. Differentiation of the neural stem cell progenitor into a specific neuron subtype depends on concerted action of intrinsic and extrinsic programs. Intrinsic regulation is achieved via combination of multiple transcription factors that are hierarchically specified during organismal development starting from establishing the anterior-posterior and dorsal-ventral polarity that creates gradients of morphogens and induces expression of gap, pair-rule and Hox genes, and subsequently assembling a set of differentially expressed transcription factors, combination of which produces the unique code for a certain neuronal subtype. This code is additionally adjusted by extrinsic cell-to-cell signaling, for example Notch for binary cell fate decision or JAK/STAT cytokine signaling for neuronal cell type specification. This unique code constantly changes in response to internal and external conditions that coordinate the development of the whole organism. Hormones are great temporal code candidates, as they direct all major developmental steps. The combination of spatial and temporal codes in neuronal precursors allows certain types of neurons to be born at exact place and time, which is critical for brain morphogenesis. For normal brain function, these neurons must cluster and synapse in a stereotyped fashion, which predominantly depends on selective cell adhesion. As a result of establishment of brain compartments and differential neuronal connections, functional neural circuits are created that process all kinds of information and control behavior, learning, memory and plasticity of each individual.