Takahashi Kaoru, Liu Fu-Chin, Hirokawa Katsuiku, Takahashi Hiroshi
Developmental Neurobiology Group, Mitsubishi Kagaku Institute of Life Sciences, Tokyo, Japan.
J Neurosci Res. 2008 Nov 1;86(14):3106-16. doi: 10.1002/jnr.21770.
Many members of the Fox family are transcription factors that regulate the morphogenesis of various organs. In the present study, we examined the expression pattern of Foxp4, a member of the Foxp subfamily, and compared its pattern with the patterns of Foxp2 and Foxp1 in the developing rat brain. In general, these three Foxp genes shared partially overlapping and yet differentially regulated expression patterns in the striatum, the cerebral cortex, and the thalamus during development. In the developing dorsal telencephalon, a mediolateral gradient of Foxp4 was present in the cortical primordium, with high levels in the ventricular zone of the medial cortex. By contrast, no gradient of Foxp2 and Foxp1 was detected in the dorsal telencephalon. At later stages, Foxp4 was expressed throughout all cortical layers as opposed to the layer-specific expression of Foxp2 and Foxp1. In the developing striatum, the pattern of Foxp4 expression was distinct from the patterns of Foxp2 and Foxp1. The spatial expression pattern of Foxp4 was similar to that of Foxp2 during the early embryonic stage. However, from the late embryonic stage to postnatal day 4, Foxp4 was expressed in a mediolateral gradient and decreased in the striosomal compartment, in contrast to the striosomal expression of Foxp2 and homogeneous expression of Foxp1. Foxp4 was developmentally down-regulated such that Foxp4 was undetectable in the forebrain after postnatal day 14, whereas Foxp2 and Foxp1 were persistently expressed in adulthood. Given that Foxp4, Foxp2, and Foxp1 are capable of heterodimerization for transcriptional regulation, the partially overlapping expression patterns of Foxp4, Foxp2, and Foxp1 in different domains of the developing forebrain suggest that each member and/or different combinatory actions of the Foxp subfamily may play a pivotal role in regulating forebrain development.
Fox家族的许多成员都是调节各种器官形态发生的转录因子。在本研究中,我们检测了Foxp亚家族成员Foxp4的表达模式,并将其与发育中的大鼠脑中Foxp2和Foxp1的模式进行了比较。总体而言,这三个Foxp基因在发育过程中的纹状体、大脑皮层和丘脑中具有部分重叠但又受不同调节的表达模式。在发育中的背侧端脑,Foxp4在皮质原基中呈现出从内侧到外侧的梯度,在内侧皮质的室管膜区水平较高。相比之下,在背侧端脑中未检测到Foxp2和Foxp1的梯度。在后期阶段,Foxp4在所有皮质层中均有表达,这与Foxp2和Foxp1的层特异性表达不同。在发育中的纹状体中,Foxp4的表达模式与Foxp2和Foxp1的模式不同。在胚胎早期阶段,Foxp4的空间表达模式与Foxp2相似。然而,从胚胎后期到出生后第4天,Foxp4以从内侧到外侧的梯度表达,并在纹状小体区域减少,这与Foxp2在纹状小体中的表达以及Foxp1的均匀表达相反。Foxp4在发育过程中表达下调,以至于在出生后第14天之后在前脑中无法检测到,而Foxp2和Foxp1在成年期持续表达。鉴于Foxp4、Foxp2和Foxp1能够通过异源二聚化进行转录调控,Foxp4、Foxp2和Foxp1在发育中的前脑不同区域的部分重叠表达模式表明,Foxp亚家族的每个成员和/或不同的组合作用可能在调节前脑发育中起关键作用。