Here, for the first time, we detailed the spatiotemporal expression pattern of IL3 and its receptors in developing mouse brain and we found IL3RA is mainly expressed in neural progenitors and neurons, which also support the importance of IL3 signaling pathway in brain development. Also, our in vitro proliferation and survival assays further validate the pivotal roles of IL3 in the development of central nervous system. Collectively, these results provide novel insights to the involvement of IL3 in brain development, supporting the neurodevelopmental hypothesis of schizophrenia. It should be noted that during the initial screening in the Chinese sample, we used cranial volume as proxy of brain volume. Though cranial volume is not exactly equal to brain volume, the correlation between these two variables is very high. More importantly, we have successfully identified the association between cranial volume and MCPH1 gene by applying this method in our previous study. In addition, the successful replication of our initial findings in genetically divergent Butenafine hydrochloride populations further support the reliability of our method. Hence, the functional data suggests rs31480 is probably the causal SNP in brain volume regulation. Nevertheless, we have successfully replicated the significant Orbifloxacin associations of IL3 variants with brain volume in BIG sample, and we also observed a marginal significant association in CBDB/NIMH sample. Although the association of these SNPs did not reach genome-wide significance, considering the non-overlap of the studied samples and different genetic backgrounds of Chinese and Europeans, IL3 is likely an authentic gene contributing to brain volume variation in general populations. To date, no genes have been shown significantly associated with brain volume and only a few genes were associated with intracranial volume in recent genome-wide association studies, suggesting an extremely complicated genetic regulation of brain volume. Growing evidence have suggested that the interaction between immune and nervous systems may play an important role in the pathogenesis of schizophrenia. The immune and nervous systems interact with each other through cytokines, a family of proteins that are secreted by a specific group of cells of the immune system and have pleiotropic effects on many cell types, including proliferation, differentiation, and survival. IL-3 is a cytokine that induces growth and differentiation of hematopoietic stem cells and a variety of cell types originating in the bone marrow. Recent studies have demonstrated the important role of IL3 in the central nervous system. It is expressed in the hippocampus and cortices of normal mouse brain, and it stimulates the growth and proliferation of microglial cells. Studies also found that IL3 facilitates the survival of sensory neurons significantly and stimulates the formation of the neural network. In addition, IL-3 has been found to be able to promote the process extension of cultured cholinergic and prevent delayed neuronal death in the hippocampus. In fact, rat interleukin 3 receptor bsubunit was cloned from cultured microglia, and disruption of IL3 production in brain led to neurologic dysfunction. All of these studies strongly suggest that IL3 is a pivotal protective factor for CNS. More importantly, Chen et al. recently reported that IL3 was significantly associated with brain disease such as schizophrenia in three independent Irish samples.