Whitney Osceola, Voyles Tawni, Hara Erina, Chen Qianqian, White Stephanie A, Wright Timothy F
Department of Biology, New Mexico State University, Las Cruces, New Mexico, 88003.
Interdepartmental Program of Molecular, Cellular, and Integrative Physiology, UCLA, Los Angeles, California, 90095.
Dev Neurobiol. 2015 Jul;75(7):778-90. doi: 10.1002/dneu.22247. Epub 2014 Nov 26.
The forkhead domain FOXP2 and FOXP1 transcription factors are implicated in several cognitive disorders with language deficits, notably autism, and thus play a central role in learned vocal motor behavior in humans. Although a similar role for FoxP2 and FoxP1 is proposed for other vertebrate species, including songbirds, the neurodevelopmental expression of these genes are unknown in a species with lifelong vocal learning abilities. Like humans, budgerigars (Melopsittacus undulatus) learn new vocalizations throughout their entire lifetime. Like songbirds, budgerigars have distinct brain nuclei for vocal learning, which include the magnocellular nucleus of the medial striatum (MMSt), a basal ganglia region that is considered developmentally and functionally analogous to Area X in songbirds. Here, we used in situ hybridization and immunohistochemistry to investigate FoxP2 and FoxP1 expression in the MMSt of juvenile and adult budgerigars. We found FoxP2 mRNA and protein expression levels in the MMSt that were lower than the surrounding striatum throughout development and adulthood. In contrast, FoxP1 mRNA and protein had an elevated MMSt/striatum expression ratio as birds matured, regardless of their sex. These results show that life-long vocal plasticity in budgerigars is associated with persistent low-level FoxP2 expression in the budgerigar MMSt, and suggests the possibility that FoxP1 plays an organizational role in the neurodevelopment of vocal motor circuitry. Thus, developmental regulation of the FoxP2 and FoxP1 genes in the basal ganglia appears essential for vocal mimicry in a range of species that possess this relatively rare trait.
叉头框结构域FOXP2和FOXP1转录因子与多种伴有语言缺陷的认知障碍有关，尤其是自闭症，因此在人类习得的发声运动行为中起着核心作用。尽管有人提出FoxP2和FoxP1在包括鸣禽在内的其他脊椎动物物种中也有类似作用，但在具有终身发声学习能力的物种中，这些基因的神经发育表达情况尚不清楚。与人类一样，虎皮鹦鹉（Melopsittacus undulatus）一生都在学习新的发声。与鸣禽一样，虎皮鹦鹉有专门用于发声学习的脑核，其中包括内侧纹状体大细胞核（MMSt），这是一个基底神经节区域，在发育和功能上被认为与鸣禽的X区类似。在这里，我们使用原位杂交和免疫组织化学方法来研究幼年和成年虎皮鹦鹉MMSt中FoxP2和FoxP1的表达。我们发现，在整个发育过程和成年期，MMSt中FoxP2的mRNA和蛋白质表达水平均低于周围的纹状体。相比之下，随着鸟类成熟，无论性别如何，FoxP1的mRNA和蛋白质在MMSt/纹状体中的表达比值都会升高。这些结果表明，虎皮鹦鹉终身发声可塑性与MMSt中持续低水平的FoxP2表达有关，并提示FoxP1在发声运动神经回路的神经发育中可能起组织作用。因此，基底神经节中FoxP2和FoxP1基因的发育调控对于一系列具有这种相对罕见特征的物种的发声模仿似乎至关重要。
