脑组织某些区域组织结构上的性双态性在脊椎动物中普遍存在，雌、雄两性间这些脑区的差异会最终导致动物个体的相关行为出现巨大差异，其中最为显著的当属鸣禽的鸣唱系统。一般情况下，鸣禽只有雄性个体才能学会鸣唱，而雌性个体不能，相应的控制鸣唱行为的发声控制核团也具有显著的性别差异。HVC是鸣禽发声控制核团的最高级中枢，它的核团体积、神经元数目、大小、神经投射等表型均具有显著的雌雄差异。不仅如此，HVC可能还通过直接或间接的神经联系来调节、甚至控制其他发声核团的性双态发育。但目前为止，HVC核团的性双态发育形成的过程、其内在的神经生物学调节机制等问题尚不清楚。本课题首先通过放射状胶质细胞纤维的标记以及VZ区损毁等实验确定了幼年白腰文鸟孵化以后HVC神经元在VZ区的主要发源位点及其细胞迁移路径；在此基础上分析了HVC细胞数目性别差异的形成过程（细胞增殖、迁移、还是分化）；之后通过离体培养实验对HVC性双态发育的调节因素进行分析，并在肯定了雌激素对HVC性双态发育调节作用的基础上，分析了雌二醇调节HVC性双态发育的可能机制。我们的结果显示：⑴ 幼鸟孵化后HVC新生细胞主要起源于覆盖在其上方的VZ区，随后沿放射状胶质细胞纤维迁移至HVC；⑵HVC细胞在增殖、迁移、分化方面的性别差异是HVC神经元数目性双态产生的重要原因；⑶雄性脑组织分泌或合成的一些脑源性因子（如雌激素）能促成HVC的雄性化发育；⑷雌二醇能促进P15白腰文鸟HVC对应VZ区内神经干细胞的增殖，以及神经元的分化，并进一步发现雌二醇的这方面作用可能是通过上调HVC区域内BDNF的表达而实现的；⑸雌二醇能调节P15幼鸟HVC区域内BDNF基因的表达，但对其受体trkB的表达无影响，说明激素并非控制HVC的性双态发育的唯一因素，而可能是与其他非激素因子共同起作用；⑹我们还发现，与已报道的成年金丝雀HVC中的调节机制不同，在幼年白腰文鸟HVC中E2对BDNF表达的调节与VEGF以及上皮细胞并无关系，而有可能是通过ER直接调节BDNF的表达。

Sexually dimorphic brain areas had been documented in a variety of vertebrates, of which the brain areas controlling song learning and production in oscine species show some of the most robust sexual differences yet studied in vertebrates. In most songbirds, only males produce courtship song, and correspondingly, song control nuclei in males possess larger and several time more neurons than in females. Among all song control nuclei, HVC is the most crucial nucleus and may be responsible for the sexual dimorphism of the whole song control circuit. However, the mechanism underling the sexually dimorphic development of HVC is still unclear. The present series of experiments tried to perform a comprehensive analysis of whether cellular proliferation within the VZ, cell migration, and/or specification take effect on sex differences of the net addition of HVC neurons in vivo, based on the location of an important subregion of VZ from which HVC neurons originate as well as the migratory route; then analyzed whether HVC sexual dimorphism developed independent of gonadal hormones, attempted as well to address the role of estrogen during sexual differentiation of HVC in vitro and the probable mechanism. We show (1) most HVC newborn cells of posthatchling Bengalese finches are derived from the subregion VZ that above the putative HVC area, and migrate along radial glia fibers to the area of HVC; (2) the sexual dimorphism of HVC cells in aspects of proliferation, migration and early differentiation are accouted for sex difference of HVC; and (3) slices culture of putative HVC shows that this dimorphism could develop independently of direct action of gonadal steroids, and that brain-autonomous mechanisms involved in the sexually dimorphic development of HVC; (4) Furthermore, we demonstrate that E2 induced the sex differentiation of HVC in vitro, and probably by up-regulation of the brain-derived neurotrophic factor (BDNF) expression; (5) E2 could regulate the expression of BDNF, but has no influence on expression its receptor, trkB, indicating that there are other mechanisms except estrogens modulating the sexually dimorphic development of HVC; (6) at last, we claimed that VEGF and endothelial cells did not involve in E2-induced BDNF up-regulation in HVC of juvenile Bengalese finches as in HVC of adult female canaries, and suggested that E2 may regulate the transcription of BDNF directly by means of ER.