Zhou L, Hashimi H, Schwartz L M, Nambu J R
Biology Department, University of Massachusetts at Amherst 01003, USA.
Curr Biol. 1995 Jul 1;5(7):784-90. doi: 10.1016/s0960-9822(95)00155-2.
During the development of the central nervous system, large numbers of cells die by programmed cell death. This process requires the activity of specific gene products and subserves functions that include regulating the sizes of interacting cell populations and removing cells that provide transient functions. Resolution of programmed cell death often involves the elimination of dying cell corpses by phagocytic macrophages. In Drosophila, the reaper gene plays a crucial role in mediating programmed cell death; chromosomal deficiencies which remove reaper result in an absence of programmed cell death. We have used a reaper-deficiency mutant strain Df(3R)H99 (or H99), in conjunction with strains containing cell-type-specific markers, to examine the role of programmed cell death in differentiation of the embryonic central nervous system midline.
Midline cell death was identified both by the presence of excess midline cells in H99 mutants and by the engulfment of dying midline cells by macrophages in wild-type embryos. These developmental deaths are lineage-specific: prominent midline glial death was observed, while little if any death was detected among the ventral unpaired median neurons. Examination of H99 mutants indicates that cell death is not required for the formation of macrophage precursors, or for their subsequent migration throughout the embryo; however, in the absence of dying cells, macrophage precursors do not exhibit morphological differentiation or phagocytosis. In both wild-type and H99 mutant embryos, a subset of macrophages migrate along the ventral midline. This midline migration is not observed in single-minded mutants, in which ventral midline cells fail to develop.
Programmed cell death plays a crucial role in the development of the central nervous system midline, and dying midline cells are rapidly eliminated by phagocytic macrophages. It seems that the generation of engulfment signals in cells undergoing programmed cell death is downstream of reaper gene function, and that central nervous system midline and/or ventral epidermal cells provide directional cues for migrating macrophages.
在中枢神经系统发育过程中，大量细胞通过程序性细胞死亡而死亡。这一过程需要特定基因产物的活性，并服务于多种功能，包括调节相互作用的细胞群体大小以及清除具有短暂功能的细胞。程序性细胞死亡的解决通常涉及吞噬性巨噬细胞清除垂死的细胞尸体。在果蝇中，收割者基因在介导程序性细胞死亡中起关键作用；去除收割者基因的染色体缺失会导致程序性细胞死亡缺失。我们使用了收割者基因缺失突变体菌株Df(3R)H99（或H99），结合含有细胞类型特异性标记的菌株，来研究程序性细胞死亡在胚胎中枢神经系统中线分化中的作用。
通过H99突变体中中线细胞过多以及野生型胚胎中巨噬细胞对垂死中线细胞的吞噬来确定中线细胞死亡。这些发育性死亡具有谱系特异性：观察到明显的中线神经胶质细胞死亡，而在腹侧不成对中间神经元中几乎未检测到死亡。对H99突变体的检查表明，细胞死亡对于巨噬细胞前体的形成或其随后在整个胚胎中的迁移并非必需；然而，在没有垂死细胞的情况下，巨噬细胞前体不会表现出形态分化或吞噬作用。在野生型和H99突变体胚胎中，都有一部分巨噬细胞沿腹侧中线迁移。在单-minded突变体中未观察到这种中线迁移，在该突变体中腹侧中线细胞无法发育。
程序性细胞死亡在中枢神经系统中线发育中起关键作用，垂死的中线细胞会被吞噬性巨噬细胞迅速清除。似乎在经历程序性细胞死亡的细胞中吞噬信号的产生是在收割者基因功能的下游，并且中枢神经系统中线和/或腹侧表皮细胞为迁移的巨噬细胞提供了定向线索。
