Zhang Wenjun, Yatskievych Tatiana A, Baker Robert K, Antin Parker B
Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA.
Dev Biol. 2004 Apr 15;268(2):312-26. doi: 10.1016/j.ydbio.2004.01.019.
The vertebrate liver and heart arise from adjacent cell layers in the anterior lateral (AL) endoderm and mesoderm of late gastrula embryos, and the earliest stages of liver and heart development are interrelated through reciprocal tissue interactions. Although classical embryological studies performed several decades ago in chick and quail defined the timing of hepatogenic induction in birds and the important role for cardiogenic mesoderm in this process, almost nothing is known about the molecular aspects of avian liver development. Here we use in vivo and explantation assays to investigate tissue interactions and signaling pathways regulating Hex, a homeobox gene required for liver development, and the earliest stages of hepatogenesis in the chick embryo. We find that explants of late gastrula anterior lateral endoderm plus mesoderm, which have been used extensively for studies relating to heart development, also produce albumin-expressing hepatoblasts. Expression of Hex, the earliest known molecular marker for the hepatogenic endoderm, and albumin, indicative of early committed hepatoblasts, requires both autocrine Bmp signaling and a specific paracrine signal from the cardiogenic (anterior lateral) mesoderm. Endodermal expression of Fox2a, in contrast, requires the mesoderm but is independent of Bmp signaling. In vivo induction assays show that the ability of BMP2 to activate Hex expression in the endoderm is restricted to a region that is only slightly larger than the endogenous domain of Hex expression. Although Fgfs can substitute for the cardiogenic mesoderm to support the expression of Hex and albumin in the endoderm, several Fgf genes are expressed in the anterior lateral endoderm but an Fgf expressed predominantly in the mesoderm was not identified. Studies also showed that Fgf gene expression in the endoderm does not require a signal from the mesoderm. Mechanisms regulating endodermal signaling pathways activated by Fgfs may therefore be more complex than previously appreciated.
脊椎动物的肝脏和心脏起源于原肠胚晚期胚胎前外侧（AL）内胚层和中胚层的相邻细胞层，肝脏和心脏发育的最早阶段通过相互的组织相互作用相互关联。尽管几十年前在鸡和鹌鹑身上进行的经典胚胎学研究确定了鸟类肝源性诱导的时间以及心脏中胚层在此过程中的重要作用，但对于鸟类肝脏发育的分子方面几乎一无所知。在这里，我们使用体内和外植体试验来研究调节Hex（肝脏发育所需的一个同源框基因）的组织相互作用和信号通路，以及鸡胚肝脏发生的最早阶段。我们发现，广泛用于心脏发育相关研究的原肠胚晚期前外侧内胚层加中胚层的外植体，也能产生表达白蛋白的肝母细胞。Hex（肝源性内胚层最早已知的分子标记）和白蛋白（表明早期定向肝母细胞）的表达既需要自分泌Bmp信号，也需要来自心脏（前外侧）中胚层的特定旁分泌信号。相比之下，Fox2a在内胚层的表达需要中胚层，但独立于Bmp信号。体内诱导试验表明，BMP2激活内胚层中Hex表达的能力仅限于一个仅略大于Hex表达内源性区域的区域。尽管Fgfs可以替代心脏中胚层来支持内胚层中Hex和白蛋白的表达，但几个Fgf基因在前外侧内胚层中表达，但未鉴定出主要在中胚层表达的Fgf。研究还表明，内胚层中Fgf基因的表达不需要来自中胚层信号。因此，调节由Fgfs激活的内胚层信号通路的机制可能比以前认为得更复杂。
