Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67400 Illkirch, France.
Centre National de la Recherche Scientifique, UMR7104, 67400 Illkirch, France.
J Neurosci. 2019 Jan 9;39(2):238-255. doi: 10.1523/JNEUROSCI.1059-18.2018. Epub 2018 Nov 30.
Despite their different origins, glia and hemocytes are related cell populations that provide an immune function. hemocytes patrol the body cavity and act as macrophages outside the nervous system, whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the immune cells within (glia) and outside (hemocytes) the nervous system require the same transcription factor glial cells deficient/glial cells missing (Glide/Gcm) for their development. This raises the issue of how do glia specifically differentiate in the nervous system, and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and panglial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us to understand the bases of cell specification. Both sexes were analyzed. Distinct cell types often require the same pioneer transcription factor, raising the issue of how one factor triggers different fates. In , glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the glial cells deficient/glial cells missing (Glide/Gcm) transcription factor, glia originate from the ectoderm, and hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification.
尽管胶质细胞和血细胞起源不同，但它们是具有免疫功能的相关细胞群。血细胞在体腔中巡逻，在神经系统外充当巨噬细胞，而胶质细胞则起源于神经上皮，为神经系统提供清道夫细胞。因此，胶质细胞是脊椎动物小胶质细胞的功能同源物，尽管后者是免疫起源的细胞，随后在发育过程中迁移到大脑中。有趣的是，神经系统内（胶质细胞）和外（血细胞）的免疫细胞都需要相同的转录因子胶质细胞缺失/胶质细胞缺失（Glide/Gcm）来发育。这就提出了一个问题，即胶质细胞如何在神经系统中特异性分化，而血细胞又如何在前脑原肠胚中分化。已知 Repo 同源域转录因子和 Glide/Gcm 的泛神经胶质直接靶标可确保胶质细胞的终末分化。在这里，我们表明 Repo 也在区分胶质细胞和血细胞的过程中发挥了核心作用。首先，Mesoderm 特异性因子抑制血细胞原基中的 Repo 表达。其次，在前脑原肠胚中异位激活 Repo 足以抑制血细胞特异性基因的表达。第三，缺乏 Repo 会触发胶质细胞中血细胞标记物的表达。因此，一个复杂的组织特异性线索网络会影响 Glide/Gcm 的潜力。这些数据使我们能够修改命运决定因素的概念，并帮助我们理解细胞特化的基础。对两性进行了分析。不同的细胞类型通常需要相同的先驱转录因子，这就提出了一个问题，即一个因子如何触发不同的命运。在这里，胶质细胞和血细胞分别在神经系统内外提供清道夫活性。虽然它们都需要胶质细胞缺失/胶质细胞缺失（Glide/Gcm）转录因子，但胶质细胞起源于外胚层，血细胞起源于中胚层。在这里，我们表明组织特异性因子通过抑制 Glide/Gcm 的同源域蛋白 Repo 的表达来抑制 Glide/Gcm 在中胚层中的神经发生潜力，Repo 是 Glide/Gcm 的主要神经胶质靶标。反过来，Repo 表达抑制了神经系统中血细胞特异性基因的表达。这些细胞特异性网络仅在神经系统中确保胶质细胞命运的建立，并允许细胞多样化。
