Combinatorial interactions of Serpent, Lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis
Combinatorial interactions of Serpent, Lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis
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DOI：
10.1073/pnas.1635050100
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发表时间：
2003-09-30
影响因子：
11.1
通讯作者：
Schulz, RA
中科院分区：
文献类型：
--
作者：
Fossett, N;Hyman, K;Schulz, RA
加塔因子Serpent（Srp）是果蝇造血过程中血细胞前体形成所必需的。这些血细胞祖细胞在发育中的胚胎中产生两种不同的谱系。菱形，Runx蛋白同源物，和神经胶质细胞缺失-1和-2是必不可少的晶体细胞和浆细胞的生产，分别。相反，U形，一个朋友的加塔类因素，拮抗晶体细胞的形成。在这里，我们表明，Srp，菱形和U形的相互作用在不同的组合，以调节晶体细胞谱系承诺。Srp和菱形的共表达协同激活晶体细胞程序在胚胎和幼虫阶段。此外，表达菱形和cDNANC，一个Srp亚型与N-和C-末端锌指，抑制U形的表达，这表明晶体细胞的激活与此阻遏物编码基因的下调相一致。相比之下，而U形和cDNANC一起阻止晶体细胞的生产，U形与非相互作用的Srp蛋白的共表达未能防止这种血细胞群体的过度生产。这些结果表明，U形和CNONC必须相互作用，以阻止晶体细胞的产生。两者合计，这些研究表明，专门的cDNANC异构体在晶体细胞谱系的承诺，作为一个激活剂或抑制剂取决于特定的转录辅助调节剂的可用性发挥了关键作用。这些研究结果提供了明确的证据，在果蝇和体内演示的加塔和Runx功能的相互作用，在血细胞的承诺程序的造血组合调节。
The GATA factor Serpent (Srp) is required for hemocyte precursor formation during Drosophila hematopoiesis. These blood cell progenitors give rise to two distinct lineages within the developing embryo. Lozenge, a Runx protein homologue, and Glial cells missing-1 and -2 are essential for crystal cell and plasmatocyte production, respectively. In contrast U-shaped, a Friend of GATA class factor, antagonizes crystal cell formation. Here we show that Srp, Lozenge, and U-shaped interact in different combinations to regulate crystal cell lineage commitment. Coexpression of Srp and Lozenge synergistically activated the crystal cell program in both embryonic and larval stages. Furthermore, expression of Lozenge and SrpNC, a Srp isoform with N- and C-terminal zinc fingers, inhibited u-shaped expression, indicating that crystal cell activation coincided with the down-regulation of this repressor-encoding gene. In contrast, whereas U-shaped and SrpNC together blocked crystal cell production, coexpression of U-shaped with noninteracting Srp proteins failed to prevent overproduction of this hemocyte population. Such results indicated that U-shaped and SrpNC must interact to block crystal cell production. Taken together, these studies show that the specialized SrpNC isoform plays a pivotal role during crystal cell lineage commitment, acting as an activator or repressor depending on the availability of specific transcriptional coregulators. These findings provide definitive proof of the combinatorial regulation of hematopoiesis in Drosophila and an in vivo demonstration of GATA and Runx functional interaction in a blood cell commitment program.