Takashima Shigeo, Yoshimori Haruka, Yamasaki Naoyuki, Matsuno Kenji, Murakami Ryutaro
Department of Physics, Biology, and Informatics, Yamaguchi University, Yamaguchi 753-8512, Japan.
Dev Genes Evol. 2002 Dec;212(11):534-41. doi: 10.1007/s00427-002-0262-z. Epub 2002 Oct 3.
The Drosophila large intestine is initially subdivided into dorsal and ventral domains with distinct cell types, and a one-cell-wide strand of boundary cells is induced between them. Here we show that cell identity and localization of the boundary cells are determined by the combined action of Delta, Notch, and engrailed genes. The prospective dorsal domain of the hindgut primordium expresses engrailed. Engrailed represses Delta, which is ubiquitously expressed throughout the prospective hindgut region in early blastodermal stages, in the dorsal domain, and thus generates a Delta-positive/negative prepattern. Expression of Engrailed protein determines the dorsal domain, while an Engrailed-negative (Delta-positive) region is differentiated into the ventral domain. Delta-positive ventral cells activate a Notch cascade in abutting dorsal cells, and thus induce their differentiation into boundary cells. Mis-expression of a constitutively active Notch intracellular domain causes the entire large intestine to develop as boundary cells. It was also found that the transducing activity of a transmembrane form of activated Notch, which requires further proteolytic processing to generate intracellular fragments, is suppressed in the Delta-positive domain. Delta acts in two distinct ways: it activates the Notch signaling pathway in adjacent Delta-negative cells, and, at the same time, autonomously blocks Notch signaling in Delta-positive cells by affecting Notch processing.
果蝇的大肠最初被细分为具有不同细胞类型的背侧和腹侧区域，并且在它们之间诱导形成一条单细胞宽的边界细胞链。在这里我们表明，边界细胞的细胞身份和定位是由Delta、Notch和engrailed基因的联合作用决定的。后肠原基的预期背侧区域表达engrailed。Engrailed抑制Delta，Delta在早期囊胚阶段在整个预期后肠区域普遍表达，在背侧区域被抑制，从而产生Delta阳性/阴性的前模式。Engrailed蛋白的表达决定了背侧区域，而Engrailed阴性（Delta阳性）区域分化为腹侧区域。Delta阳性的腹侧细胞在相邻的背侧细胞中激活Notch级联反应，从而诱导它们分化为边界细胞。组成型活性Notch细胞内结构域的错误表达导致整个大肠发育为边界细胞。还发现，需要进一步蛋白水解加工以产生细胞内片段的跨膜形式的活化Notch的转导活性在Delta阳性区域受到抑制。Delta以两种不同的方式起作用：它在相邻的Delta阴性细胞中激活Notch信号通路，同时，通过影响Notch加工在Delta阳性细胞中自主阻断Notch信号。
