Gupta Ishita, Yeung Joanna, Rahimi-Balaei Maryam, Wu Sih-Rong, Goldowitz Dan
British Columbia Children's Hospital, Vancouver, BC, Canada.
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Front Mol Neurosci. 2024 Apr 29;17:1356544. doi: 10.3389/fnmol.2024.1356544. eCollection 2024.
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 genes, a family of three transcription factors, that are expressed downstream of Bone Morphogenetic Protein (BMP) signaling in these zones. Using fluorescent RNA hybridization, we have characterized the (Msh Homeobox) genes and demonstrated that their spatiotemporal pattern segregates specific regions within the progenitor zones. and are compartmentalized within the rhombic lip (RL), while is localized within the ventricular zone (VZ). The relationship of the genes with an early marker of the glutamatergic lineage, , was examined in -null mice and it was found that the expression of genes persisted. Importantly, the spatial expression of and altered in response to the elimination of . 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, .
在小脑原基早期,存在两个祖细胞区,即位于第四脑室顶部的脑室区(VZ)和发育中小脑外侧边缘的菱唇(RL)。这些区域分别产生构成成年小脑GABA能和谷氨酸能神经元群体的几种细胞类型。最近,人们对这些区域的分子分隔有了一定的认识。为了丰富这一知识库,我们报道了Msx基因,这是一个由三个转录因子组成的家族,它们在这些区域的骨形态发生蛋白(BMP)信号下游表达。利用荧光RNA杂交技术,我们对Msx(Msh同源框)基因进行了表征,并证明它们的时空模式将祖细胞区内的特定区域分隔开来。Msx1和Msx2在菱唇(RL)内分隔,而Msx3定位于脑室区(VZ)。在Msx1基因敲除小鼠中研究了Msx基因与谷氨酸能谱系早期标志物Lhx2的关系,发现Msx基因的表达持续存在。重要的是,Msx1和Msx2的空间表达因Lhx2的缺失而改变。这些结果表明Msx基因是小脑祖细胞区新的早期标志物,更重要的是,相对于菱唇的经典标志物Lhx2,它更新了我们对菱唇分子分隔的认识。
Front Mol Neurosci. 2024-4-29
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