The role of Notch signaling and its regulators in temporal specification of neural progenitor cells

Background Notch-mediated signaling is involved in the proliferation and differentiation of almost all types of cells[such as neural precursor cell (NPC)], and plays a key role in cell-fate determination and developmental regulation in vertebrates and invertebrates. Notch signaling pathway is involved in the self-renewal of NPC and the differentiation of types of neurons. Objective To discuss the role of Notch signaling pathway and the mechanisms underlying its regulation of temporal specification of NPC. Content In Notch signaling pathway, the ligand, Delta/Serrate/Lag-2(DSL), binds to the receptor, Notch, and initiates two steps enzymatic incision, resulting in the internalization of Notch intracellular domain(NICD), the latter binds to CBF1/Su(H)/Lag-1 (CSL) DNA binding protein, and recruits several transcription factors to regulate the expression of downstream genes, including Hairy/enhancer of split(Hes) and nuclear factor 1 A(NF1A). During neurogenesis, Notch signaling pathway upregulates Hes1 to maintain non-differentiation status of NPC, inhibiting neurogenesis. In neuron transition period, NF1A binds glial fibrillary acidic protein(GFAP), triggers the expression of GFAP, and promotes the differentiation of NPC. During gliogenesis, NF1A and Hes1 interacts to form a feedback loop to control the differentiation of astrocytes. Neurons and glial cells have several molecules regulate Notch signaling pathways by targeting the ligand, the receptor, and Hes1/NF1A, to maintain the homeostasis of the nervous system. Trend The canonical Notch signaling pathway plays pivotal roles in regulating NPC with precise temporal specification. Exposure to some general anesthetic agents during the fetal period has been shown to induce detrimental effects in temporal specification of NPC in the embryonic nervous system and persistent learning and memory deficits. It suggests that Notch signaling pathway might be a potential target of anesthetic agents to confer their developmental neurotoxicity. Key words: Neural progenitor cell; Temporal specification; Notch signaling pathway