Institute of Genetics, Queens Medical Centre, University of Nottingham, NG7 2UH, UK.
Dev Biol. 2010 Jul 1;343(1-2):138-52. doi: 10.1016/j.ydbio.2010.04.002. Epub 2010 Apr 13.
Understanding how mesoderm is specified during development is a fundamental issue in biology, and it has been studied intensively in embryos from Xenopus. The gene regulatory network (GRN) for Xenopus is surprisingly complex and is not conserved in vertebrates, including mammals, which have single copies of the key genes Nodal and Mix. Why the Xenopus GRN should express multiple copies of Nodal and Mix genes is not known. To understand how these expanded gene families evolved, we investigated mesoderm specification in embryos from axolotls, representing urodele amphibians, since urodele embryology is basal to amphibians and was conserved during the evolution of amniotes, including mammals. We show that single copies of Nodal and Mix are required for mesoderm specification in axolotl embryos, suggesting the ancestral vertebrate state. Furthermore, we uncovered a novel genetic interaction in which Mix induces Brachyury expression, standing in contrast to the relationship of these molecules in Xenopus. However, we demonstrate that this functional relationship is conserved in mammals by showing that it is involved in the production of mesoderm from mouse embryonic stem cells. From our results, we produced an ancestral mesoderm (m)GRN, which we suggest is conserved in vertebrates. The results are discussed within the context of a theory in which the evolution of mechanisms governing early somatic development is constrained by the ancestral germ line-soma relationship, in which germ cells are produced by epigenesis.
理解中胚层在发育过程中是如何特化的是生物学中的一个基本问题,在非洲爪蟾胚胎中对此进行了深入研究。非洲爪蟾的基因调控网络(GRN)非常复杂,在包括哺乳动物在内的脊椎动物中并不保守,哺乳动物只有单个 Nodal 和 Mix 关键基因的拷贝。为什么非洲爪蟾的 GRN 应该表达多个 Nodal 和 Mix 基因的拷贝尚不清楚。为了了解这些扩展的基因家族是如何进化的,我们研究了代表有尾两栖类的蝾螈胚胎中的中胚层特化,因为有尾两栖类的胚胎学在两栖动物中是基础的,并且在包括哺乳动物在内的羊膜动物的进化中是保守的。我们表明,单个 Nodal 和 Mix 拷贝对于蝾螈胚胎中的中胚层特化是必需的,这表明了祖先脊椎动物的状态。此外,我们发现了一个新的遗传相互作用,其中 Mix 诱导 Brachyury 的表达,与 Xenopus 中这些分子的关系形成对比。然而,我们通过证明它参与了从小鼠胚胎干细胞中产生中胚层,证明了这种功能关系在哺乳动物中是保守的。根据我们的结果,我们产生了一个祖先中胚层(m)GRN,我们认为它在脊椎动物中是保守的。这些结果是在一个理论框架内讨论的,该理论认为,早期体节发育的机制进化受到祖先生殖系-体节关系的限制,在这种关系中,生殖细胞是通过胚胎发生产生的。