Resolving embryonic blood cell fate choice in Drosophila:: interplay of GCM and RUNX factors

Resolving embryonic blood cell fate choice in Drosophila:: interplay of GCM and RUNX factors
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DOI:
10.1242/dev.02034
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发表时间:
2005-10-01
期刊:
影响因子:
4.6
通讯作者:
Waltzer, L
Waltzer, L
中科院分区:
生物学2区
文献类型:
--
作者:
Bataillé, L;Augé, B;Waltzer, L

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果蝇胚胎造血祖细胞(原血细胞)向浆细胞或晶体细胞的分化受谱系特异性转录因子控制。相关蛋白Glial cells missing (GCM)和GCM2控制浆细胞的发育,而RUNX因子Lozenge (LZ)是晶体细胞分化所必需的。我们研究了导致这两种细胞类型形成的分离过程,以及LZ和GCM/GCM2之间的相互作用。我们发现,令人惊讶的是,gcm最初在所有的原血细胞中表达,但在最前面的原血细胞中迅速下调,然后启动lz的表达。然而,lz+祖先构成了一个混合谱系群体,其命运取决于lz和GCM/GCM2的相对水平。值得注意的是,我们证明了GCM/GCM2通过抑制lz的激活和维持,在控制晶体细胞群的大小方面发挥了关键作用。此外,我们发现原血细胞是双能祖细胞,gcm/gcm(2)的下调是lz诱导的晶体细胞形成所必需的。这些结果为果蝇造血控制机制提供了新的见解,并为解决血细胞命运选择的原始模型奠定了基础。
The differentiation of Drosophila embryonic blood cell progenitors (prohemocytes) into plasmatocytes or crystal cells is controlled by lineage-specific transcription factors. The related proteins Glial cells missing (GCM) and GCM2 control plasmatocyte development, whereas the RUNX factor Lozenge (LZ) is required for crystal cell differentiation. We have investigated the segregation process that leads to the formation of these two cell types, and the interplay between LZ and GCM/GCM2. We show that, surprisingly, gcm is initially expressed in all prohemocytes but is rapidly downregulated in the anterior-most row of prohemocytes, which then initiates lz expression. However, the lz+ progenitors constitute a mixed-lineage population whose fate depends on the relative levels of LZ and GCM/GCM2. Notably, we demonstrate that GCM/GCM2 play a key role in controlling the size of the crystal cell population by inhibiting lz activation and maintenance. Furthermore, we show that prohemocytes are bipotent progenitors, and that downregulation of gcm/gcm(2) is required for lz-induced crystal cell formation. These results provide new insight into the mechanisms controlling Drosophila hematopoiesis and establish the basis for an original model for the resolution of the choice of blood cell fate.