Mesman Simone, Krüse Sonja J, Smidt Marten P
Swammerdam Institute for Life Sciences, FNWI University of Amsterdam, The Netherlands.
Swammerdam Institute for Life Sciences, FNWI University of Amsterdam, The Netherlands.
Gene Expr Patterns. 2018 Jan;27:8-15. doi: 10.1016/j.gep.2017.09.001. Epub 2017 Sep 27.
Mesodiencephalic dopaminergic (mdDA) neurons are born in the ventricular zone (VZ) of the midbrain between E10 and E12. Although these neurons all express specific DA markers like Th and Pitx3, they are subdivided into distinct subsets, each depending on a unique set of transcription factors and signaling cascades for their differentiation. How a neural progenitor commits to an mdDA neuronal cell-fate and how the specification into the different subsets is determined remains unclear. To gain more insight into the development and specification of these neurons we have previously conducted a genome-wide expression analysis, in which dissected midbrain material (E10.5-E13.5) was compared to the adult mdDA region (Chakrabarty et al., 2012). In the present study, we have compared the genome-wide expression analysis including PITX3-GFP sorted (E12.5-E15.5) neurons to available expression data to search for genes specifically expressed in the midbrain during early stages of mdDA differentiation. We have divided these genes into 3 groups: (I) genes upregulated throughout differentiation (Mest, NeuroD1, and Tcf12), (II) genes upregulated during early stages of differentiation (Hes5, and Tcf3), and (III) genes upregulated during late stages of differentiation (Enc1). Here, we show the expression profile of these genes in the embryonic midbrain during development and adult stage and compared that to the appearance of mdDA neurons via co-staining for TH. With this analysis we have identified 6 novel factors that may play a role during cell-fate commitment of neural progenitors or later during differentiation of the mdDA group of neurons.
中脑多巴胺能（mdDA）神经元在胚胎第10天至12天之间于中脑的脑室区（VZ）产生。尽管这些神经元都表达特定的多巴胺标记物，如酪氨酸羟化酶（Th）和垂体转录因子3（Pitx3），但它们被细分为不同的亚群，每个亚群在分化过程中依赖于一组独特的转录因子和信号级联反应。神经祖细胞如何决定成为mdDA神经元细胞命运以及如何确定分化为不同亚群仍不清楚。为了更深入了解这些神经元的发育和分化，我们之前进行了全基因组表达分析，将解剖的中脑材料（胚胎第10.5天至13.5天）与成年mdDA区域进行比较（Chakrabarty等人，2012年）。在本研究中，我们将包括PITX3-GFP分选的（胚胎第12.5天至15.5天）神经元的全基因组表达分析与可用的表达数据进行比较，以寻找在mdDA分化早期阶段在中脑特异性表达的基因。我们将这些基因分为3组：（I）在整个分化过程中上调的基因（中胚层特异性转录本，神经分化因子1，转录因子12），（II）在分化早期上调的基因（毛状分裂增强子同源物5，转录因子3），以及（III）在分化后期上调的基因（上皮细胞转化基因1）。在此，我们展示了这些基因在胚胎中脑发育和成年阶段的表达谱，并通过酪氨酸羟化酶共染色将其与mdDA神经元的出现进行比较。通过这项分析，我们确定了6个新的因子，它们可能在神经祖细胞的细胞命运决定过程中或在mdDA神经元组的后期分化过程中发挥作用。
