Rodaway A, Takeda H, Koshida S, Broadbent J, Price B, Smith J C, Patient R, Holder N
Developmental Biology Research Centre, Randall Institute, King's College London, London, WC2B 5RL, UK.
Development. 1999 Jun;126(14):3067-78. doi: 10.1242/dev.126.14.3067.
The endoderm forms the gut and associated organs, and develops from a layer of cells which emerges during gastrula stages in the vertebrate embryo. In comparison to mesoderm and ectoderm, little is known about the signals which induce the endoderm. The origin of the endoderm is intimately linked with that of mesoderm, both by their position in the embryo, and by the molecules that can induce them. We characterised a gene, zebrafish gata5, which is expressed in the endoderm from blastula stages and show that its transcription is induced by signals originating from the yolk cell. These signals also induce the mesoderm-expressed transcription factor no tail (ntl), whose initial expression coincides with gata5 in the cells closest to the blastoderm margin, then spreads to encompass the germ ring. We have characterised the induction of these genes and show that ectopic expression of activin induces gata5 and ntl in a pattern which mimics the endogenous expression, while expression of a dominant negative activin receptor abolishes ntl and gata5 expression. Injection of RNA encoding a constitutively active activin receptor leads to ectopic expression of gata5 and ntl. gata5 is activated cell-autonomously, whereas ntl is induced in cells distant from those which have received the RNA, showing that although expression of both genes is induced by a TGF-beta signal, expression of ntl then spreads by a relay mechanism. Expression of a fibroblast growth factor (eFGF) or a dominant negatively acting FGF receptor shows that ntl but not gata5 is regulated by FGF signalling, implying that this may be the relay signal leading to the spread of ntl expression. In embryos lacking both squint and cyclops, members of the nodal group of TGF-beta related molecules, gata5 expression in the blastoderm is abolished, making these factors primary candidates for the endogenous TGF-beta signal inducing gata5.
内胚层形成肠道及相关器官，它由脊椎动物胚胎原肠胚阶段出现的一层细胞发育而来。与中胚层和外胚层相比，诱导内胚层形成的信号鲜为人知。内胚层的起源与中胚层的起源紧密相连，这既体现在它们在胚胎中的位置，也体现在能够诱导它们的分子上。我们鉴定了一个基因——斑马鱼gata5，它从囊胚期开始就在内胚层中表达，并且表明其转录是由源自卵黄细胞的信号诱导的。这些信号还诱导中胚层表达的转录因子无尾（ntl），其最初的表达与gata5在最接近胚盘边缘的细胞中一致，然后扩散至整个胚环。我们已经对这些基因的诱导过程进行了鉴定，结果表明，激活素的异位表达以模仿内源性表达的模式诱导gata5和ntl的表达，而显性负性激活素受体的表达则消除了ntl和gata5的表达。注射编码组成型活性激活素受体的RNA会导致gata5和ntl的异位表达。gata5是细胞自主激活的，而ntl是在远离那些接受了RNA的细胞中被诱导表达的，这表明尽管这两个基因的表达都是由TGF-β信号诱导的，但ntl的表达随后通过一种中继机制扩散。成纤维细胞生长因子（eFGF）或显性负性作用的FGF受体的表达表明，ntl受FGF信号调控，而gata5不受其调控，这意味着这可能是导致ntl表达扩散的中继信号。在缺乏与TGF-β相关分子的结节组成员斜视和独眼的胚胎中，胚盘中gata5的表达被消除，这使得这些因子成为诱导gata5的内源性TGF-β信号的主要候选者。
