Rayburn Lowell Y M, Rhea Jeanne, Jocoy Steven R, Bender Michael
Department of Genetics, The University of Georgia, Athens, GA 30602, USA.
Dev Biol. 2009 Sep 1;333(1):48-56. doi: 10.1016/j.ydbio.2009.06.021. Epub 2009 Jun 25.
Peptide hormones governing many developmental processes are generated via endoproteolysis of inactive precursor molecules by a family of subtilisin-like proprotein convertases (SPCs). We previously identified mutations in the Drosophila amontillado (amon) gene, a homolog of the vertebrate neuroendocrine-specific Prohormone Convertase 2 (PC2) gene, and showed that amon is required during embryogenesis, early larval development, and larval molting. Here, we define amon requirements during later developmental stages using a conditional rescue system and find that amon is required during pupal development for head eversion, leg and wing disc extension, and abdominal differentiation. Immuno-localization experiments show that amon protein is expressed in a subset of central nervous system cells but does not co-localize with peptide hormones known to elicit molting behavior, suggesting the involvement of novel regulatory peptides in this process. The amon protein is expressed in neuronal cells that innervate the corpus allatum and corpora cardiaca of the ring gland, an endocrine organ which is the release site for many key hormonal signals. Expression of amon in a subset of these cell types using the GAL4/UAS system in an amon mutant background partially rescues larval molting and growth. Our results show that amon is required for pupal development and identify a subset of neuronal cell types in which amon function is sufficient to rescue developmental progression and growth defects shown by amon mutants. The results are consistent with a model that the amon protein acts to proteolytically process a diverse suite of peptide hormones that coordinate larval and pupal growth and development.
许多发育过程受肽类激素调控,这些肽类激素由一类枯草杆菌蛋白酶样前蛋白转化酶(SPCs)对无活性前体分子进行内切蛋白水解产生。我们之前在果蝇阿蒙蒂亚多(amon)基因中发现了突变,该基因是脊椎动物神经内分泌特异性激素原转化酶2(PC2)基因的同源物,并表明amon在胚胎发生、幼虫早期发育和幼虫蜕皮过程中是必需的。在这里,我们使用条件性拯救系统确定了amon在后期发育阶段的需求,发现amon在蛹发育过程中对头外翻、腿和翅盘伸展以及腹部分化是必需的。免疫定位实验表明,amon蛋白在中枢神经系统细胞的一个子集中表达,但不与已知引发蜕皮行为的肽类激素共定位,这表明在此过程中有新的调节肽参与。amon蛋白在支配环腺的咽侧体和心侧体的神经元细胞中表达,环腺是一个内分泌器官,是许多关键激素信号的释放部位。在amon突变背景下,使用GAL4/UAS系统在这些细胞类型的一个子集中表达amon,可部分拯救幼虫蜕皮和生长。我们的结果表明,amon是蛹发育所必需的,并确定了一组神经元细胞类型,其中amon的功能足以拯救amon突变体所表现出的发育进程和生长缺陷。这些结果与一个模型一致,即amon蛋白通过蛋白水解作用处理多种肽类激素,以协调幼虫和蛹的生长与发育。