Early patterning of ABCB, ABCC, and ABCG transporters establishes unique territories of small molecule transport in embryonic mesoderm and endoderm.
Early patterning of ABCB, ABCC, and ABCG transporters establishes unique territories of small molecule transport in embryonic mesoderm and endoderm.
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DOI：
10.1016/j.ydbio.2020.12.021
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发表时间：
2021-04
影响因子：
2.7
通讯作者：
Hamdoun A
中科院分区：
文献类型：
--
作者：
Schrankel CS;Hamdoun A
多种小分子（包括代谢物、信号分子和外源分子）的定向细胞间运动是多细胞性的一个关键特征。小分子转运体（smt）网络，包括几种ATP结合盒（ABC）转运体，是这一过程的核心。虽然小分子转运蛋白在分化器官中得到了很好的描述，但对它们在早期胚胎发生中的表达模式知之甚少。在这里，我们报道了abc型SMT在海胆发育早期的表达和活性模式。在该胚胎的6种主要abc （ABCB1、-B4、-C1、-C4、-C5和-G2）中，观察到3种表达模式：1)ABCB1和ABCC1首先普遍表达，然后在内胚层和外胚层衍生结构中富集。2) ABCC4和ABCC5局限于囊胚的中胚层环，ABCC4随后在原始生殖细胞的胚位体腔囊中表达。3) ABCB4和ABCG2仅在内胚层细胞中表达。荧光底物和转运蛋白抑制剂的检测显示，ABCC4外排活性环来自ABCC4阳性中胚层细胞。同样，在进食开始之前，在发育中的肠道中观察到ABCB1和ABCB4的外排活性。这项研究揭示了在胚胎发生过程中小分子运输的独特区域的早期建立。ABCC4/C5的表达模式与肠道内陷和种系发育过程中的信号功能一致，而ABCB1/B4和ABCG2的表达模式与胚胎肠道中的作用一致。这项工作为研究SMT网络的功能和进化提供了一个概念框架，并定义了驱动这些基因表达的特定发育途径。
Directed intercellular movement of diverse small molecules, including metabolites, signal molecules and xenobiotics, is a key feature of multicellularity. Networks of small molecule transporters (SMTs), including several ATP Binding Cassette (ABC) transporters, are central to this process. While small molecule transporters are well described in differentiated organs, little is known about their patterns of expression in early embryogenesis. Here we report the pattern of ABC-type SMT expression and activity during the early development of sea urchins. Of the six major ABCs in this embryo (ABCB1, -B4, -C1, -C4, -C5 and -G2), three expression patterns were observed: 1) ABCB1 and ABCC1 are first expressed ubiquitously, and then become enriched in endoderm and ectoderm-derived structures. 2) ABCC4 and ABCC5 are restricted to a ring of mesoderm in the blastula and ABCC4 is later expressed in the coelomic pouches, the embryonic niche of the primordial germ cells. 3) ABCB4 and ABCG2 are expressed exclusively in endoderm-fated cells. Assays with fluorescent substrates and inhibitors of transporters revealed a ring of ABCC4 efflux activity emanating from ABCC4+ mesodermal cells. Similarly, ABCB1 and ABCB4 efflux activity was observed in the developing gut, prior to the onset of feeding. This study reveals the early establishment of unique territories of small molecule transport during embryogenesis. A pattern of ABCC4/C5 expression is consistent with signaling functions during gut invagination and germ line development, while a later pattern of ABCB1/B4 and ABCG2 is consistent with roles in the embryonic gut. This work provides a conceptual framework with which to examine the function and evolution of SMT networks and define the specific developmental pathways that drive the expression of these genes.
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影响因子：
14.8
作者：
Butcher RA
通讯作者：
Butcher RA
影响因子：
5.6
作者：
Engelhart, Darcy C.;Azad, Priti;Nigam, Sanjay K.
通讯作者：
Nigam, Sanjay K.
影响因子：
5.8
作者：
Cheung, Leanna;Flemming, Claudia L.;Norris, Murray D.
通讯作者：
Norris, Murray D.
影响因子：
5.4
作者：
Almen, Markus Sallman;Nordstrom, Karl J. V.;Schioth, Helgi B.
通讯作者：
Schioth, Helgi B.
影响因子：
4.1
作者：
Andrikou C;Iovene E;Rizzo F;Oliveri P;Arnone MI
通讯作者：
Arnone MI