Savage-Dunn Cathy, Yu Ling, Gill Kwesi, Awan Muhammad, Fernando Thilini
Department of Biology, Queens College, City University of New York, Flushing, NY 11367, USA.
Genet Res (Camb). 2011 Dec;93(6):427-32. doi: 10.1017/S0016672311000310.
In Caenorhabditis elegans, the Bone Morphogenetic Protein (BMP)-related ligand Dpp- and BMP-like-1 (DBL-1) regulates body size by promoting the larval and adult growth of the large epidermal syncytium hyp7 without affecting cell division. This system provides an excellent model for dissecting the growth-promoting activities of BMP ligands, since in this context the growth and differentiation functions of DBL-1 are naturally uncoupled. dbl-1 is expressed primarily in neurons and the DBL-1 ligand signals to its receptors and Smad signal transducers in the target tissue of the epidermis. The requirements constraining the source(s) of DBL-1, however, have not previously been investigated. We show here that dbl-1 expression requirements are strikingly relaxed. Expression in non-overlapping subsets of the endogenous expression pattern, as well as ectopic expression, can provide sufficient levels of activity for rescue of the small body size of dbl-1 mutants. By analysing dbl-1 expression levels in transgenic strains with different degrees of rescue, we corroborate the model that DBL-1 is a dose-dependent regulator of growth. We conclude that, for body size regulation, the site of expression of dbl-1 is less important than the level of expression.
在秀丽隐杆线虫中，骨形态发生蛋白（BMP）相关配体Dpp和BMP样蛋白1（DBL-1）通过促进大型表皮合胞体hyp7的幼虫和成虫生长来调节体型，而不影响细胞分裂。该系统为剖析BMP配体的促生长活性提供了一个极佳的模型，因为在此背景下，DBL-1的生长和分化功能自然解偶联。dbl-1主要在神经元中表达，并且DBL-1配体向其受体以及表皮靶组织中的Smad信号转导子发出信号。然而，此前尚未研究限制DBL-1来源的条件。我们在此表明，dbl-1的表达条件显著宽松。在内源表达模式的非重叠亚组中的表达以及异位表达，都可为挽救dbl-1突变体的小体型提供足够的活性水平。通过分析不同程度挽救的转基因品系中的dbl-1表达水平，我们证实了DBL-1是生长的剂量依赖性调节因子这一模型。我们得出结论，对于体型调节而言，dbl-1的表达位点不如表达水平重要。
