Zhang Gaoqun, Ferg Marco, Lübke Luisa, Takamiya Masanari, Beil Tanja, Gourain Victor, Diotel Nicolas, Strähle Uwe, Rastegar Sepand
Institute of Biological and Chemical Systems-Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Université de La Réunion, INSERM, UMR 1188, Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Saint-Denis de La Réunion, France.
Stem Cells. 2020 Jul;38(7):875-889. doi: 10.1002/stem.3182. Epub 2020 Apr 11.
In the telencephalon of adult zebrafish, the inhibitor of DNA binding 1 (id1) gene is expressed in radial glial cells (RGCs), behaving as neural stem cells (NSCs), during constitutive and regenerative neurogenesis. Id1 controls the balance between resting and proliferating states of RGCs by promoting quiescence. Here, we identified a phylogenetically conserved cis-regulatory module (CRM) mediating the specific expression of id1 in RGCs. Systematic deletion mapping and mutation of conserved transcription factor binding sites in stable transgenic zebrafish lines reveal that this CRM operates via conserved smad1/5 and 4 binding motifs under both homeostatic and regenerative conditions. Transcriptome analysis of injured and uninjured telencephala as well as pharmacological inhibition experiments identify a crucial role of bone morphogenetic protein (BMP) signaling for the function of the CRM. Our data highlight that BMP signals control id1 expression and thus NSC proliferation during constitutive and induced neurogenesis.
在成年斑马鱼的端脑中，DNA结合抑制因子1（id1）基因在作为神经干细胞（NSC）的放射状胶质细胞（RGC）中表达，这些细胞在组成性和再生性神经发生过程中发挥作用。Id1通过促进静止来控制RGC静止和增殖状态之间的平衡。在这里，我们鉴定了一个系统发育保守的顺式调控模块（CRM），它介导id1在RGC中的特异性表达。在稳定的转基因斑马鱼品系中对保守转录因子结合位点进行系统的缺失作图和突变分析表明，该CRM在稳态和再生条件下均通过保守的smad1/5和4结合基序发挥作用。对受伤和未受伤端脑的转录组分析以及药理学抑制实验确定了骨形态发生蛋白（BMP）信号传导对CRM功能的关键作用。我们的数据表明，BMP信号在组成性和诱导性神经发生过程中控制id1表达，从而控制神经干细胞增殖。
