Abstract:
In the early cerebellar primordium, there are two progenitor zones, the ventricular zone (VZ) residing atop the IVth ventricle and the rhombic lip (RL) at the lateral edges of the developing cerebellum. These zones give rise to the several cell types that form the GABAergic and glutamatergic populations of the adult cerebellum, respectively. Recently, an understanding of the molecular compartmentation of these zones has emerged. To add to this knowledge base, we report on the Msx genes, a family of three transcription factors, that are expressed downstream of Bone Morphogenetic Protein (BMP) signaling in these zones. Using fluorescent RNA in situ hybridization, we have characterized the Msx (Msh Homeobox) genes and demonstrated that their spatiotemporal pattern segregates specific regions within the progenitor zones. Msx1 and Msx2 are compartmentalized within the rhombic lip (RL), while Msx3 is localized within the ventricular zone (VZ). The relationship of the Msx genes with an early marker of the glutamatergic lineage, Atoh1, was examined in Atoh1-null mice and it was found that the expression of Msx genes persisted. Importantly, the spatial expression of Msx1 and Msx3 altered in response to the elimination of Atoh1. These results point to the Msx genes as novel early markers of cerebellar progenitor zones and more importantly to an updated view of the molecular parcellation of the RL with respect to the canonical marker of the RL, Atoh1.
摘要:
在早期小脑原基,有两个祖先区,位于第IV个心室顶部的心室区(VZ)和发育中的小脑侧边缘的菱形唇(RL)。这些区域产生了形成成年小脑的GABA能和谷氨酸能群体的几种细胞类型,分别。最近,对这些区域的分子分隔的理解已经出现。要添加到此知识库,我们报道了Msx基因,一个由三个转录因子组成的家族,在这些区域的骨形态发生蛋白(BMP)信号的下游表达。使用荧光RNA原位杂交,我们对Msx(MshHomeobox)基因进行了表征,并证明了它们的时空模式隔离了祖细胞区内的特定区域。Msx1和Msx2被分隔在菱形唇(RL)内,而Msx3位于心室区(VZ)内。Msx基因与谷氨酸能谱系早期标记的关系,在Atoh1-null小鼠中检查Atoh1,发现Msx基因的表达持续存在。重要的是,Msx1和Msx3的空间表达响应于Atoh1的消除而改变。这些结果表明,Msx基因是小脑祖细胞区的新型早期标记,更重要的是,相对于RL的规范标记,RL的分子分裂得到了更新。Atoh1.