Requirement for Pdx1 in specification of latent endocrine progenitors in zebrafish.
Requirement for Pdx1 in specification of latent endocrine progenitors in zebrafish.
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DOI：
10.1186/1741-7007-9-75
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发表时间：
2011-10-31
期刊：
影响因子：
5.4
通讯作者：
Meyer D
中科院分区：
文献类型：
--
作者：
Kimmel RA;Onder L;Wilfinger A;Ellertsdottir E;Meyer D
在胰腺发育过程中，产生胰岛素的β细胞以两个连续的波出现。最近描述的斑马鱼后期形成的β细胞在发育能力上与第二波哺乳动物β细胞高度相似。小鼠和斑马鱼的功能丧失研究表明，同源盒转录因子Pdx1和Hb9对胰腺和β细胞的发育都至关重要，并且已经发现了这些基因的离散阶段特异性需求。以前，研究表明斑马鱼的外分泌和内分泌细胞会随着pdx1的缺失而恢复，但有关的祖细胞和分子机制尚未明确定义。此外，pdx1和hb9在β细胞形成中的相互作用尚未得到解决。为了了解更多关于内分泌祖细胞规格的信息，我们研究了在morpholinos介导的pdx1和hb9缺失后β细胞的形成。我们发现，在早期β细胞减少后，在pdx1或hb9功能丧失后会出现恢复。出乎意料的是，同时敲低hb9和pdx1会导致几乎完全和持续的β细胞缺陷。我们使用NeuroD:EGFP转基因细胞系来检测体内内分泌细胞的行为，并开发了一种新的实时成像技术来实时记录晚期形成的内分泌前体的出现和迁移。我们的数据显示，晚期内分泌细胞的notch应答祖细胞主要发生在有丝分裂后，并依赖于pdx1。相比之下，早期产生的内分泌细胞是独立于pdx1的特异性和分化的。hb9和pdx1联合缺失后几乎完全的β细胞缺失表明功能合作，我们阐明了其在早期和晚期内分泌细胞形成中的不同作用。一种新的成像方法首次允许在发育中的胚胎中可视化晚期内分泌细胞的出现。我们证明了pdx1依赖性祖细胞群对导管相关的第二波内分泌细胞的形成至关重要。我们进一步揭示了这些祖细胞的有丝分裂活性出乎意料地低，表明它们在发育早期被搁置。
Insulin-producing beta cells emerge during pancreas development in two sequential waves. Recently described later-forming beta cells in zebrafish show high similarity to second wave mammalian beta cells in developmental capacity. Loss-of-function studies in mouse and zebrafish demonstrated that the homeobox transcription factors Pdx1 and Hb9 are both critical for pancreas and beta cell development and discrete stage-specific requirements for these genes have been uncovered. Previously, exocrine and endocrine cell recovery was shown to follow loss of pdx1 in zebrafish, but the progenitor cells and molecular mechanisms responsible have not been clearly defined. In addition, interactions of pdx1 and hb9 in beta cell formation have not been addressed. To learn more about endocrine progenitor specification, we examined beta cell formation following morpholino-mediated depletion of pdx1 and hb9. We find that after early beta cell reduction, recovery occurs following loss of either pdx1 or hb9 function. Unexpectedly, simultaneous knockdown of both hb9 and pdx1 leads to virtually complete and persistent beta cell deficiency. We used a NeuroD:EGFP transgenic line to examine endocrine cell behavior in vivo and developed a novel live-imaging technique to document emergence and migration of late-forming endocrine precursors in real time. Our data show that Notch-responsive progenitors for late-arising endocrine cells are predominantly post mitotic and depend on pdx1. By contrast, early-arising endocrine cells are specified and differentiate independent of pdx1. The nearly complete beta cell deficiency after combined loss of hb9 and pdx1 suggests functional cooperation, which we clarify as distinct roles in early and late endocrine cell formation. A novel imaging approach permitted visualization of the emergence of late endocrine cells within developing embryos for the first time. We demonstrate a pdx1-dependent progenitor population essential for the formation of duct-associated, second wave endocrine cells. We further reveal an unexpectedly low mitotic activity in these progenitor cells, indicating that they are set aside early in development.
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影响因子：
11.8
作者：
Chung, Won-Suk;Shin, Chong Hyun;Stainier, Didier Y. R.
通讯作者：
Stainier, Didier Y. R.
DOI：
10.1073/pnas.97.22.11984
发表时间：
2000-10-24
影响因子：
11.1
作者：
Baird, GS;Zacharias, DA;Tsien, RY
通讯作者：
Tsien, RY
影响因子：
64.8
作者：
Apelqvist, Å;Li, H;Edlund, H
通讯作者：
Edlund, H
影响因子：
2.5
作者：
Langenberg, T;Brand, M;Cooper, MS
通讯作者：
Cooper, MS
影响因子：
2.7
作者：
Gannon, Maureen;Ables, Elizabeth Tweedie;Wright, Christopher V. E.
通讯作者：
Wright, Christopher V. E.