胚胎巨噬细胞和小胶质细胞消融调控小鼠胚胎背根神经节感觉神经元的发育

Embryonic macrophages and microglia ablation alter the development of dorsal root ganglionsensory neurons in mouse embryos

众所周知,小胶质细胞可以调节中枢神经系统发育的一些方面。在第11.5天的小鼠胚胎中的小胶质细胞定殖脊髓时,它们与背根神经节感觉神经元(SN)的生长中心轴突相互作用,这表明它们可能在SN发育中发挥一定功能。为了解决这个问题,我们使用缺乏胚胎巨噬细胞(PU.1敲除小鼠)和免疫细胞消融的小鼠胚胎分析胚胎巨噬细胞消融对SNs早期发育的影响。我们发现,除小胶质细胞外,胚胎巨噬细胞还与来自第11.5天的小鼠胚胎的原肌球蛋白受体激酶(Trk)C+感觉神经元,TrkB+感觉神经元和TrkA+感觉神经元外周神经突产生交联。免疫细胞剥夺会导致第11.5天的小鼠胚胎的TrkC+感觉神经元和TrkB+感觉神经元初始数量的减少,这与其发育细胞死亡(DCD)的改变有关联的可能性较小,因为其后在第12.5天的胚胎中的数量有短暂增加。在分析的发育期(第11.5~15.5天),它也导致TrkA+感觉神经元数量减少,尽管我们没有观察到他们的DCD有任何变化。与神经元祖细胞可能存在一致性的脑脂肪酸结合蛋白(BFABP-)阴性细胞的增殖在第11.5天的胚胎中增加,而它们的增殖在第12.5天的胚胎减少,这可部分解释从11.5 d观察到的SN亚型产生的改变。此外,我们观察到在缺乏胚胎巨噬细胞的情况下神经胶质细胞祖细胞(BFABP+细胞)增殖的改变。我们的数据表明,胚胎巨噬细胞和小胶质细胞消融调控SN的发育。

Microglia are known to regulate several aspects of the development of the central nervous system. When microglia colonize the spinal cord, from El 1.5 in the mouse embryo, they interact with growing central axons of dorsal root ganglion sensory neurons （SNs）, which suggests that they may have some functions in SN development. To address this issue, we analyzed the effects of embryonic macrophage ablation on the earlydevelop-ment of SNs using mouse embryo lacking embryonic macrophages （PU.l knock-out mice） and immune cell ablation. We discovered that, in addition to microglia, embryonic macrophages contact tropomyosin receptor kinase （Trk） C＋ SN, TrkB＋ SN, and TrkA＋ SN peripheral neurites from El 1.5. Deprivation of immune cells resulted in an initial reduction of TrkC＋ SN and TrkB＋ SN populations at Ell.5 that was unlikely to be related to an alteration in their developmental cell death （DCD）, followed by a transitory increase in their number at E12.5. It also resulted in a reduction of TrkA＋ SN number during the developmental period analyzed （E 11.5 ～E15.5）, although we did not observe any change in their DCD. Proliferation of cells negative for brain fatty acid-binding protein （BFABP- ）, which likely correspond to neuronal progenitors, was increased at Ell.5, while their proliferation was decreased at E12.5, which could partly explain the alterations of SN subtype production observed from El 1.5. In addition, we observed alterations in the proliferation of glial cell progenitors （BFABP＋ cells） in the absence of embryonic macrophages. Our data indicate that embryonic macrophages and microglia ablation alter the development of SNs.