Genome-wide analysis of the genes differentially expressed between neuronal progenitor and the differentiated neuronal cells FTY720 revealed that all three members of the TAM family are expressed in the embryonic cortical neuronal progenitor cells. Mice lacking both Axl and Mertk caused early differentiation and migration of SVZ NSCs, and knockout of their common ligand, Gas6, reduced the NSC numbers in the SVZ. These evidences indicate that TAM receptors might play important roles in maintenance of the cortical neuronal progenitor cell identity, in regulation of the NSCs survival, proliferation, and differentiation. In the present study, we demonstrated that the primary NSCs express all three members of the TAM receptors to provide trophic support for themselves to ensure the survival, proliferation and differentiation into immature neurons in vitro. Under normal culture condition, TKO NSCs showed a significant reduction in NGF expression, accompanied by compensational increases in the expression of TrkA, TrkB and TrkC, suggesting that the TAM receptors function in coordination with neurotrophins in NSCs. Intrinsic trophic support by the TAM receptor signaling pathway on the NSCs may represent a novel signaling pathway in adult neural stem cells maintenance and differentiation. We have recently shown that mice lacking the TAM receptors displayed impaired adult hippocampal neurogenesis. All three of the TAM receptors are expressed by microglia and astrocytes; and knockout of all three Tyro3, Axl and Mertk genes, caused both cell types to exhibit enhanced innate immune responses to TLR activation and to produce higher levels of proinflammatory cytokines detrimental to NSC self-renewal and neuronal differentiation. In addition, several lines of evidence showed that all three receptors were expressed in hippocampus, especially in the subgranular layer of the DG, as demonstrated by in situ hybridization. However, whether or not they are expressed in hippocampal neural stem cells is not clear. In the present study, we performed Western blot and immunostaining analysis of Tyro3, Axl and Mertk in the primary cultured NSCs, and found that those cells expressed all three receptors. Based on these receptors’ growth trophic roles in many cell types, we hypothesized that the TAM receptors might also play intrinsic tropic functions in the NSCs. This was true that the primary cultured TKO NSCs versus their WT counterparts exhibited slower growth rate, decreased proliferation, and survival capacity, as demonstrated by poor BrdU incorporation and increased TUNEL labeling, respectively. These observations strongly suggest that TAM receptors provide trophic support for NSCs proliferation and survival. On the other hand, studies on the Axl and Mertk double knockout mice showed that embryonic SVZ NSCs in the double mutant embryos exhibited early differentiation and migration. The TKO NSCs in our suspension culture system might undergo premature differentiation resulting in lower growth and proliferation rate and smaller sphere size. Recent studies indicate that TAM receptors function in NSCs.