Evolutionary origins of lymphocytes: Ensembles of T cell and B cell transcriptional regulators in a cartilaginous fish

Evolutionary origins of lymphocytes: Ensembles of T cell and B cell transcriptional regulators in a cartilaginous fish
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DOI:
10.4049/jimmunol.172.10.5851
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发表时间:
2004-05-15
影响因子:
4.4
通讯作者:
Rothenberg, EV
Rothenberg, EV
中科院分区:
医学2区
文献类型:
--
作者:
Anderson, MK;Pant, R;Rothenberg, EV

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淋巴细胞的进化起源可以通过关键特征的系统发育比较来追踪。重排 TCR 和 Ig(B 细胞受体)基因的同源物存在于有颌脊椎动物中,但尚未在其他动物群体中发现。相比之下,哺乳动物 T 和 B 淋巴细胞发育所必需的大多数转录因子属于多基因家族,这些家族以大多数后生动物的成员为代表,为通向前脊椎动物祖先角色提供了潜在的桥梁。这项工作研究了已知调节哺乳动物 T 和 B 细胞发育的特定转录因子同源物的结构和调节,这些转录因子是最早的分叉有颌脊椎动物的代表,即透明鼻鳐鱼 (Raja eglanteria)。哺乳动物 GATA-3、GATA-1、EBF-1、Pax-5、Pax-6、Runx2 和 Runx3 的 Skate 直系同源物已得到表征。 GATA-3、Pax-5、Runx3、EBF-1、Spi-C 和 Ikaros 家族的大多数成员在整个个体发育过程中显示为 1) 与 TCR 或 Ig 表达共同调节,2) 彼此以组合方式共表达,大部分对应于已知的小鼠 T 和 B 细胞模式,支持功能保守。这些结果表明,在哺乳动物 T 细胞和 B 细胞发育中起作用的基因调控网络的多个组件存在于哺乳动物和软骨鱼的共同祖先中。然而,与 B 谱系相关的某些因子的组织特异性表达模式与小鼠对应物不同,表明这些动物中 B 谱系特征或组织特异性有所扩展或不同。
The evolutionary origins of lymphocytes can be traced by phylogenetic comparisons of key features. Homologs of rearranging TCR and Ig (B cell receptor) genes are present in jawed vertebrates, but have not been identified in other animal groups. In contrast, most of the transcription factors that are essential for the development of mammalian T and B lymphocytes belong to multigene families that are represented by members in the majority of the metazoans, providing a potential bridge to prevertebrate ancestral roles. This work investigates the structure and regulation of homologs of specific transcription factors known to regulate mammalian T and B cell development in a representative of the earliest diverging jawed vertebrates, the clearnose skate (Raja eglanteria). Skate orthologs of mammalian GATA-3, GATA-1, EBF-1, Pax-5, Pax-6, Runx2, and Runx3 have been characterized. GATA-3, Pax-5, Runx3, EBF-1, Spi-C, and most members of the Ikaros family are shown throughout ontogeny to be 1) coregulated with TCR or Ig expression, and 2) coexpressed with each other in combinations that for the most part correspond to known mouse T and B cell patterns, supporting conservation of function. These results indicate that multiple components of the gene regulatory networks that operate in mammalian T cell and B cell development were present in the common ancestor of the mammals and the cartilaginous fish. However, certain factors relevant to the B lineage differ in their tissue-specific expression patterns from their mouse counterparts, suggesting expanded or divergent B lineage characteristics or tissue specificity in these animals.