Department of Neuroscience, Developmental Biology Center and Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Neural Dev. 2011 Nov 11;6:35. doi: 10.1186/1749-8104-6-35.
The size and cell number of each brain region are influenced by the organization and behavior of neural progenitor cells during embryonic development. Recent studies on developing neocortex have revealed the presence of neural progenitor cells that divide away from the ventricular surface and undergo symmetric divisions to generate either two neurons or two progenitor cells. These 'basal' progenitor cells form the subventricular zone and are responsible for generating the majority of neocortical neurons. However, not much has been studied on similar types of progenitor cells in other brain regions.
We have identified and characterized basal progenitor cells in the embryonic mouse thalamus. The progenitor domain that generates all of the cortex-projecting thalamic nuclei contained a remarkably high proportion of basally dividing cells. Fewer basal progenitor cells were found in other progenitor domains that generate non-cortex projecting nuclei. By using intracellular domain of Notch1 (NICD) as a marker for radial glial cells, we found that basally dividing cells extended outside the lateral limit of radial glial cells, indicating that, similar to the neocortex and ventral telencephalon, the thalamus has a distinct subventricular zone. Neocortical and thalamic basal progenitor cells shared expression of some molecular markers, including Insm1, Neurog1, Neurog2 and NeuroD1. Additionally, basal progenitor cells in each region also expressed exclusive markers, such as Tbr2 in the neocortex and Olig2 and Olig3 in the thalamus. In Neurog1/Neurog2 double mutant mice, the number of basally dividing progenitor cells in the thalamus was significantly reduced, which demonstrates the roles of neurogenins in the generation and/or maintenance of basal progenitor cells. In Pax6 mutant mice, the part of the thalamus that showed reduced Neurog1/2 expression also had reduced basal mitosis.
Our current study establishes the existence of a unique and significant population of basal progenitor cells in the thalamus and their dependence on neurogenins and Pax6. These progenitor cells may have important roles in enhancing the generation of neurons within the thalamus and may also be critical for generating neuronal diversity in this complex brain region.
每个脑区的大小和细胞数量都受到胚胎发育过程中神经祖细胞的组织和行为的影响。最近对发育中的新皮质的研究揭示了存在从脑室表面分裂并进行对称分裂以产生两个神经元或两个祖细胞的神经祖细胞。这些“基底”祖细胞形成室下区，负责产生大多数新皮质神经元。然而，对于其他脑区中类似类型的祖细胞，研究还不多。
我们已经鉴定并描绘了胚胎期小鼠丘脑中的基底祖细胞。产生所有皮质投射丘脑核的祖细胞区域含有极高比例的基底分裂细胞。在产生非皮质投射核的其他祖细胞区域中，基底祖细胞较少。通过使用 Notch1（NICD）的细胞内结构域作为放射状胶质细胞的标记，我们发现基底分裂细胞延伸到放射状胶质细胞的外侧限之外，表明类似于新皮质和腹侧端脑，丘脑有一个明显的室下区。新皮质和丘脑的基底祖细胞共同表达一些分子标记物，包括 Insm1、Neurog1、Neurog2 和 NeuroD1。此外，每个区域的基底祖细胞也表达了独特的标记物，如新皮质中的 Tbr2 和丘脑中的 Olig2 和 Olig3。在 Neurog1/Neurog2 双突变小鼠中，丘脑基底分裂祖细胞的数量显著减少，这表明神经生成素在基底祖细胞的产生和/或维持中发挥作用。在 Pax6 突变小鼠中，显示减少的 Neurog1/2 表达的丘脑部分也减少了基底有丝分裂。
我们目前的研究确立了丘脑中存在独特且重要的基底祖细胞群体，它们依赖于神经生成素和 Pax6。这些祖细胞可能在增强丘脑内神经元的产生方面发挥重要作用，并且对于产生这个复杂脑区的神经元多样性也可能至关重要。
