Waksman Institute, Rutgers University, Piscataway, New Jersey 08854.
G3 (Bethesda). 2012 Mar;2(3):393-405. doi: 10.1534/g3.111.001693. Epub 2012 Mar 1.
Blood cell development in the Drosophila lymph gland is controlled by multiple factors, most of them conserved from flies to mammals. The Drosophila homolog of vertebrate PDCD2, Zfrp8, is required in Drosophila hematopoietic stem cell development. Zfrp8 mutant larvae show a disruption of homeostasis in the lymph gland and vast lymph gland overgrowth. The loss of one copy of Zfrp8 also causes a lymph gland enlargement. This dominant phenotype can be modified by heterozygous mutations in cell-cycle genes and several genes functioning in blood development. To identify additional genes that function in hematopoiesis, we screened a collection of second and third chromosome deficiencies for modifiers of Zfrp8 heterozygous phenotype. Using deficiency mapping, available single gene mutations, and RNAi lines, we identified several novel factors required for lymph gland development and hemocyte differentiation. Distinct lymph gland phenotypes of nine of these genes are reported here for the first time. Importantly, the orthologs of four of them have a role in mammalian blood development and leukemogenesis. Our work has shown that the number of genes regulating normal blood cell development in Drosophila is much larger than expected, and that the complex molecular mechanisms regulating hemocyte differentiation are comparable to those in vertebrates.
果蝇淋巴腺中的血细胞发育受多种因素控制，其中大多数因素在从果蝇到哺乳动物的过程中都得到了保守。果蝇 PDCD2 的同源物 Zfrp8 在果蝇造血干细胞发育中是必需的。Zfrp8 突变体幼虫显示淋巴腺稳态破坏和淋巴腺过度生长。Zfrp8 的一个拷贝缺失也会导致淋巴腺增大。这种显性表型可以通过细胞周期基因的杂合突变和在血液发育中起作用的几个基因的杂合突变来修饰。为了鉴定在造血中起作用的其他基因，我们筛选了第二和第三染色体缺失体以寻找 Zfrp8 杂合表型的修饰因子。通过缺陷作图、可用的单基因突变和 RNAi 系，我们鉴定了几个新的淋巴腺发育和血细胞分化所必需的因子。这里首次报道了其中 9 个基因的独特淋巴腺表型。重要的是，其中 4 个同源基因在哺乳动物的血液发育和白血病发生中具有作用。我们的工作表明，调节果蝇正常血细胞发育的基因数量比预期的要多得多，并且调节血细胞分化的复杂分子机制与脊椎动物相当。
