Frantz G D, Weimann J M, Levin M E, McConnell S K
Department of Biological Sciences, Stanford University, California 94305.
J Neurosci. 1994 Oct;14(10):5725-40. doi: 10.1523/JNEUROSCI.14-10-05725.1994.
Within the cerebral and cerebellar cortices, neurons are organized in layers that segregate neurons with distinctive morphologies and axonal connections, and areas or regions that correspond to distinct functional domains. To explore the molecular underpinnings of pattern formation in layered regions of the CNS, we have characterized the patterns of expression of two homeodomain genes, Otx1 and Otx2, by in situ hybridization during embryonic and postnatal development in the rat. Otx1 and Otx2 are vertebrate homologs of the Drosophila gap gene orthodenticle, and are expressed during the development of the murine CNS (Simeone et al., 1992). Here we report that Otx1 mRNA is expressed in a subpopulation of neurons within cortical layers 5 and 6 during postnatal and adult life. This gene is also expressed by the precursors of deep-layer neurons within the developing cerebral ventricular zone, but is apparently downregulated by the progenitors of upper-layer neurons; Otx1 is never expressed by the neurons of layers 1-4. The spatial and temporal patterns suggest that Otx1 may play a role in the specification or differentiation of neurons in the deep layers of the cerebral cortex. Within the cerebellum, mRNAs for Otx1 and Otx2 are found within the external granular layer (EGL), but in three spatially distinct domains. During postnatal development, Otx1 is expressed within anterior cerebellar lobules; Otx2 mRNA is localized posteriorly, and a region of overlap in mid-cerebellum defines a third domain in which both genes are expressed. The boundaries of Otx1 and Otx2 expression correspond to the major functional boundaries of the cerebellum, and define the vestibulocerebellum, spinocerebellum, and pontocerebellum, respectively. Spatially restricted patterns of hybridization are observed early in postnatal life, at times that correspond roughly to the invasion of spinal and pontine afferents into the cerebellum (Arsénio-Nunes and Sotelo, 1985; Mason, 1987). These results raise the possibility that Otx1 and Otx2 play a role in cerebellar regionalization during early development.
在大脑皮层和小脑皮层中，神经元呈层状排列，这些层将具有独特形态和轴突连接的神经元分隔开来，并且这些层还对应着不同的功能区域。为了探究中枢神经系统分层区域中模式形成的分子基础，我们通过原位杂交技术，对大鼠胚胎期和出生后发育过程中两个同源异型域基因Otx1和Otx2的表达模式进行了表征。Otx1和Otx2是果蝇缺口基因orthodenticle的脊椎动物同源物，在小鼠中枢神经系统发育过程中表达（西梅奥内等人，1992年）。在此我们报告，Otx1 mRNA在出生后及成年期的皮层第5层和第6层的一部分神经元中表达。该基因在发育中的脑室区深层神经元的前体细胞中也有表达，但显然被上层神经元的祖细胞下调；Otx1在第1 - 4层的神经元中从不表达。其时空模式表明Otx1可能在大脑皮层深层神经元的特化或分化中发挥作用。在小脑中，Otx1和Otx2的mRNA存在于外颗粒层（EGL）中，但分布在三个空间上不同的区域。在出生后发育过程中，Otx1在前小脑小叶中表达；Otx2 mRNA位于后部，小脑中部的一个重叠区域定义了第三个区域，两个基因都在该区域表达。Otx1和Otx2表达的边界对应于小脑的主要功能边界，分别定义了前庭小脑、脊髓小脑和脑桥小脑。在出生后早期就观察到了空间受限的杂交模式，此时大致对应于脊髓和脑桥传入纤维侵入小脑的时间（阿尔塞尼奥 - 努内斯和索特洛，1985年；梅森，1987年）。这些结果增加了Otx1和Otx2在早期发育过程中参与小脑区域化的可能性。
