Department of Developmental Biology and Cancer Research, IMRIC, The Hebrew University, 91120 Jerusalem, Israel.
J Cell Sci. 2012 Dec 1;125(Pt 23):5811-8. doi: 10.1242/jcs.110569. Epub 2012 Sep 6.
BMP-dependent patterning in the Drosophila melanogaster wing imaginal disc serves as a paradigm to understand how morphogens specify cell fates. The observed profile of the transcriptional response to the graded signal of BMP relies upon two counter-active gradients of pMad and Brinker (Brk). This patterning model is inadequate to explain the expression of target genes, like vestigial and spalt, in lateral regions of the wing disc where BMP signals decline and Brk levels peak. Here, we show that in contrast to the reciprocal repressor gradient mechanism, where Brk represses BMP targets in medial regions, target expression in lateral regions is downregulated by BMP signalling and activated by Brk. Brk induces lateral expression indirectly, apparently through repression of a negative regulator. Our findings provide a model explaining how the expression of an established BMP target is differentially and inversely regulated along the anterior-posterior axis of the wing disc.
果蝇翅膀 imaginal 盘的 BMP 依赖性模式形成可作为理解形态发生素如何特异性指定细胞命运的范例。观察到的转录反应对 BMP 梯度信号的特征依赖于 pMad 和 Brinker（Brk）的两个拮抗梯度。这种模式形成模型不足以解释靶基因的表达，例如 vestigial 和 spalt，在翅膀盘的侧翼区域，BMP 信号下降而 Brk 水平达到峰值。在这里，我们表明，与 Brk 在中侧区域抑制 BMP 靶基因的反向抑制梯度机制相反，靶基因在侧翼区域的表达下调是由 BMP 信号诱导的，而 Brk 则激活了靶基因的表达。Brk 通过抑制负调节剂来间接诱导侧向表达。我们的发现提供了一个模型，解释了如何在翅膀盘的前-后轴上沿不同和相反的方式调节已建立的 BMP 靶基因的表达。
