The Rosetteless gene controls development in the choanoflagellate S. rosetta.
The Rosetteless gene controls development in the choanoflagellate S. rosetta.
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作者：
Levin TC;Greaney AJ;Wetzel L;King N
动物多细胞的起源可以通过将动物与它们的近亲之一——有鞭藻（Salpingoeca rosetta）进行比较来重建。就像动物从一个单细胞发育而来一样，玫瑰花的多细胞莲座也从一个创始细胞发育而来。为了研究玫瑰花的发育，我们建立了玫瑰花的正向遗传。我们发现一种名为Rosetteless的突变体的玫瑰结缺陷与一种预测的c型凝集素相关联，这是动物发育和先天免疫所需的一类信号和粘附基因。无莲座蛋白对莲座的发育至关重要，并形成细胞外层，覆盖并连接莲座中每个细胞的基极。这项研究首次提供了鞭鞭毛虫基因型和表型之间的联系，并提出了一种具有c型凝集素样结构域的蛋白质在鞭鞭毛虫和动物的最后共同祖先中调节发育的可能性。DOI: http://dx.doi.org/10.7554/eLife.04070.001所有的动物都来自一个共同的祖先，这个祖先从单细胞生活到变得更加复杂，许多细胞一起工作。起初，这样的生物很可能是由具有相同功能的细胞群组成的。最终，不同的细胞承担了不同的角色，今天的动物有许多器官系统，每一个都由专门的细胞类型组成。然而，动物的祖先是如何从单细胞过渡到多细胞的，人们知之甚少。现在，通过比较现代动物和它们的近亲——鞭毛类动物，可以重建“多细胞生物”进化的关键步骤。它们是一组水生微生物，既可以单细胞生存，也可以发育成多细胞菌落。据推测，允许鞭藻细胞形成菌落的基因与最早的动物变成多细胞细胞的基因相似。现在，Levin等人研究了一种叫做S. rosetta的鞭藻。这个物种是一个很好的选择，因为它的基因组序列已经被解码，并且相对容易诱导玫瑰葡萄细胞在独立生活或生活在称为玫瑰的球形菌落之间切换。Levin等人使用一种被称为“正向遗传学”的技术，用化学物质和x射线轰击S. rosetta细胞，将基因突变引入细胞。然后将突变的细胞生长在通常会导致蔷薇花形成蔷薇花菌落的条件下；在这些条件下继续隔离生活的细胞随后被进一步研究，因为这意味着负责菌落形成的基因发生了突变。Levin等人发现了几个不能形成玫瑰花的突变株。其中一个突变株的基因拷贝发生了改变，Levin等人将其命名为“无玫瑰”。无莲座基因产生的蛋白质类似于组织和器官中连接动物细胞的蛋白质。通常在莲座中，这种蛋白质存在于细胞外，存在于一种将菌落细胞连接在一起的分泌结构中。在无莲座突变体中，这种蛋白质经常被错误地合成，通常会出现在细胞的错误部位。Levin等人通过制造粘附在蛋白质上并干扰其功能的抗体，从而阻止玫瑰结形成，进一步证实了无玫瑰结编码蛋白的重要性。解开无莲座基因的作用是了解哪些基因使单细胞生物有可能进化成复杂的多细胞动物的重要一步。未来对罗塞塔的基因筛选有望揭示无罗塞塔是否是调节动物发育的基因和蛋白质网络的一部分，从而阐明动物的多细胞生物背后的分子机制。DOI: http://dx.doi.org/10.7554/eLife.04070.002
The origin of animal multicellularity may be reconstructed by comparing animals with one of their closest living relatives, the choanoflagellate Salpingoeca rosetta. Just as animals develop from a single cell–the zygote–multicellular rosettes of S. rosetta develop from a founding cell. To investigate rosette development, we established forward genetics in S. rosetta. We find that the rosette defect of one mutant, named Rosetteless, maps to a predicted C-type lectin, a class of signaling and adhesion genes required for the development and innate immunity in animals. Rosetteless protein is essential for rosette development and forms an extracellular layer that coats and connects the basal poles of each cell in rosettes. This study provides the first link between genotype and phenotype in choanoflagellates and raises the possibility that a protein with C-type lectin-like domains regulated development in the last common ancestor of choanoflagellates and animals. DOI: http://dx.doi.org/10.7554/eLife.04070.001 All animals descended from a common ancestor that made the leap from living as a single cell to becoming more complicated, with many cells working together. At first, such a creature would likely have been made from clusters of cells that all had the same function. Eventually, different cells took on different roles, and today animals have many organ systems, each made up of specialized cell types. How the ancestors of animals transitioned from being single celled to multicellular, however, is poorly understood. It is now possible to reconstruct key steps in the evolution of ‘multicellularity’ by comparing modern animals with their closest living relatives—the choanoflagellates. These are a group of aquatic microorganisms that can either live as single cells or develop into multicellular colonies. The genes that allow choanoflagellate cells to form colonies are hypothesized to be similar to the genes that the very first animals used to become multicellular. Now, Levin et al. have studied a choanoflagellate called S. rosetta. This species is a good choice, as its genome sequence has been decoded and it is relatively easy to induce S. rosetta cells to switch between living on their own or living in spherical colonies called rosettes. Using a technique known as ‘forward genetics’, Levin et al. bombarded S. rosetta cells with chemicals and X-rays to introduce genetic mutations into the cells. The mutated cells were then grown in conditions that would normally cause S. rosetta to form rosette colonies; the cells that continued to live in isolation in these conditions were then studied further, as this meant that mutations had occurred in the genes responsible for colony formation. Levin et al. identified several mutant S. rosetta strains that cannot form rosettes. One of these mutant strains had an altered copy of a gene that Levin et al. named rosetteless. The protein produced by the rosetteless gene is similar to proteins that connect animal cells to one another in tissues and organs. Normally in rosettes this protein is found outside of the cells, in a secreted structure that joins the cells of the colony together. In the Rosetteless mutants, the protein is often incorrectly made and typically ends up on the wrong part of the cell. Levin et al. further confirmed the importance of the rosetteless-encoded protein by creating antibodies that stick to the protein and interfere with its function, thereby blocking rosette formation. Unraveling the role of the rosetteless gene is an important step towards understanding which genes made it possible for single-celled organisms to evolve into complex multicellular animals. Future genetic screens in S. rosetta promise to reveal whether rosetteless is part of a network of genes and proteins which regulate animal development and could thus illuminate the molecular machinery behind multicellularity in the long-extinct predecessors of animals. DOI: http://dx.doi.org/10.7554/eLife.04070.002