BMP-2诱导鸡胚心脏系标记物异位表达以及对体细胞形成的影响
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BMP-2 induces ectopic expression of cardiac lineage markers and interferes with somite formation in chicken embryos
背景与目的
在果蝇中，同源盒基因的诱导和心脏的形成依赖于上覆外胚层的DPP信号。为了明确脊椎动物心脏诱导信号，我们筛选了在HH 4期鸡胚中表达的DPP同源物。在BMP家族的其他几个成员中，大多数转录本是BMP-2。
方 法
从胚胎HH期4起，心源性中胚层与BMP-2表达细胞密切联系，这些细胞最初出现在外侧中胚层，随后出现在咽内胚层的头褶形成之后。为探讨BMP-2在心脏形成中的作用，将原代培养的雏鸡胚胎植入产生BMP-2的细胞中。
结 果
BMP-2的植入导致异位心脏中胚层规格形成。BMP-2能诱导Nkx 2-5在前脑区异位表达，同时在更接近尾端也诱导GATA-4表达。但BMP-2对心脏的诱导仍不完全，因为Nkx 2-8和心脏限制性结构基因vmhc-1均未被异位诱导。BMP-2表达细胞移植到近轴中胚层附近，导致体节形成受损，阻断了PAX-3和叉头基因cfkh-1等标记基因的表达。
结 论
这些结果提示BMP-2是心源性信号复合体的一部分，参与了早期中胚层的模式形成，类似于DPP在果蝇中的作用。
原始文献摘要
Andrée B1, Duprez D, Vorbusch B, et al. BMP-2 induces ectopic expression of cardiac lineage markers and interferes with somite formation in chicken embryos. Mech Dev. 1998 Jan;70(1-2):119-31. PMID: 9510029
Abstract
In Drosophila induction of the homeobox gene tinman and subsequent heart formation are dependent on dpp signaling from overlying ectoderm. In order to define vertebrate heart-inducing signals we screened for dpp-homologues expressed in HH stage 4 chicken embryos.The majority of transcripts were found to be BMP-2 among several other members of the BMP family. From embryonic HH stage 4 onwards cardiogenic mesoderm appeared to be in close contact to BMP-2 expressing cells which initially were present in lateral mesoderm and subsequently after headfold formation in the pharyngeal endoderm. In order to assess the role of BMP-2 for heart formation,gastrulating chick embryos in New culture were implanted with BMP-2 producing cells. BMP-2 implantation resulted in ectopic cardiac mesoderm specification. BMP-2 was able to induce Nkx2–5 expression ectopically within the anterior head domain, while GATA-4 was
also induced more caudally. Cardiogenic induction by BMP-2, however remained incomplete, since neither Nkx2–8 nor the cardiac-restricted structural gene VMHC-1 became ectopically induced. BMP-2 expressing cells implanted adjacent to paraxial mesoderm resulted in impaired somite formation and blocked the expression of marker genes, such as paraxis, Pax-3, and the forkhead gene cFKH-1. These results suggest that BMP-2 is part of the complex of cardiogenic signals and is involved in the patterning of early mesoderm similar to the role of dpp in Drosophila.
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