Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
Department of Neurobiology, Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany; Sorbonne University, 21 Rue de l'École de Médecine, 75006 Paris, France.
Stem Cell Reports. 2024 Mar 12;19(3):351-365. doi: 10.1016/j.stemcr.2024.01.008. Epub 2024 Feb 15.
The expression of growth/differentiation factor (GDF) 15 increases in the ganglionic eminence (GE) late in neural development, especially in neural stem cells (NSCs). However, GDF15 function in this region remains unknown. We report that GDF15 receptor is expressed apically in the GE and that GDF15 ablation promotes proliferation and cell division in the embryonic GE and in the adult ventricular-subventricular zone (V-SVZ). This causes a transient generation of additional neuronal progenitors, compensated by cell death, and a lasting increase in the number of ependymal cells and apical NSCs. Finally, both GDF15 receptor and the epidermal growth factor receptor (EGFR) were expressed in progenitors and mutation of GDF15 affected EGFR signaling. However, only exposure to exogenous GDF15, but not to EGF, normalized proliferation and the number of apical progenitors. Thus, GDF15 regulates proliferation of apical progenitors in the GE, thereby affecting the number of ependymal cells and NSCs.
生长/分化因子 15（GDF15）的表达在神经发育后期的神经节隆起（GE）中增加，特别是在神经干细胞（NSC）中。然而，该区域中 GDF15 的功能仍不清楚。我们报告 GDF15 受体在 GE 的顶端表达，并且 GDF15 缺失可促进胚胎 GE 和成年脑室下区（V-SVZ）中的增殖和细胞分裂。这导致额外的神经元祖细胞的短暂产生，通过细胞死亡得到补偿，并且室管膜细胞和顶端 NSC 的数量持续增加。最后，GDF15 受体和表皮生长因子受体（EGFR）都在祖细胞中表达，并且 GDF15 的突变影响 EGFR 信号。然而，仅暴露于外源性 GDF15（而不是 EGF）可使增殖和顶端祖细胞的数量正常化。因此，GDF15 调节 GE 中顶端祖细胞的增殖，从而影响室管膜细胞和 NSC 的数量。
