Stem cells have two fundamental properties: self-renewal and multipotency. Self-renewal is a cooperative process involving the proliferation and maintenance of an undifferentiated state. The loss of self-renewal properties leads to loss in multipotency, differentiation, and a change in cell fates. Therefore, self-renewal is tightly controlled by the dynamic interplay between intrinsic genetic factors (transcription factors, microRNA, and epigenetic control) and extrinsic factors from the microenvironments (niches) in which stem cells are generated, migrated, and located [1
]. Among regulatory factors involved in self-renewal, FGF-2 – which primarily acts via the FGF receptor 1 (FGFR1) – is a well-known extrinsic factor maintaining the self-renewal ability of neural stem cells [5
]. Neural stem cells are found in the adult brain as well as in developing brains, which suggests the essential roles of neurogenesis in adult brain functions [7
]. Neurogenesis occurs in response to various environmental signals, such as injury, learning, and memory, or pathological stimuli, which contribute to the remodeling of brain tissues, homeostasis, and regeneration of tissues after an injury [8
Many extrinsic factors such as EGF, VEGF, Wnt, Shh, receptor tyrosine kinases, and FGF-2 have been implicated in the self-renewal and differentiation of neural stem cells [11
]. Adult neurogenesis depends greatly on FGF-2 signaling [12
]. Although the studies on FGF-2 and its role in the maintenance or differentiation of neural stem cells are extensive, the mechanism by which FGFR signaling regulates self-renewal as well as the downstream signaling pathways contributing to the regulation of self-renewal in adult neural stem cells are not well elucidated thus far.
Ma et al. [13
] have addressed these important issues by characterizing the differential roles of MAPK and PLCγ1 in FGFR1 signaling in the self-renewal of neural stem cells by using a chimeric TrkA-FGFR1.