Homeoprotein hhex-induced conversion of intestinal to ventral pancreatic precursors results in the formation of giant pancreata in Xenopus embryos

被引:11
作者
Zhao, Hui [3 ]
Han, Dandan [2 ,5 ]
Dawid, Igor B. [1 ]
Pieler, Tomas [4 ]
Chen, Yonglong [2 ]
机构
[1] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA
[2] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China
[3] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China
[4] Univ Gottingen, Ctr Mol Biosci, Dept Dev Biochem, D-37077 Gottingen, Germany
[5] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
基金
美国国家卫生研究院;
关键词
endoderm regionalization; endocrine; exocrine; proliferation; apoptosis; HOMEOBOX GENE HEX; PROGENITOR CELLS; MOUSE EMBRYO; MORPHOGENETIC MOVEMENTS; ENDODERM DEVELOPMENT; SIGNALING PATHWAYS; WNT/BETA-CATENIN; LIVER BUD; FATE MAPS; DIFFERENTIATION;
D O I
10.1073/pnas.1206547109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Liver and ventral pancreas develop from neighboring territories within the endoderm of gastrulae. ventral pancreatic precursor 1 (vpp1) is a marker gene that is differentially expressed in a cell population within the dorsal endoderm in a pattern partially overlapping with that of hematopoietically expressed homeobox (hhex) during gastrulation. In tail bud embryos, vpp1 expression specifically demarcates two ventral pancreatic buds, whereas hhex expression is mainly restricted to the liver diverticulum. Ectopic expression of a critical dose of hhex led to a greatly enlarged vpp1-positive domain and, subsequently, to the formation of giant ventral pancreata, putatively by conversion of intestinal to ventral pancreatic precursor cells. Conversely, antisense morpholino oligonucleotide-mediated knockdown of hhex resulted in a down-regulation of vpp1 expression and a specific loss of the ventral pancreas. Furthermore, titration of hhex with a dexamethasone-inducible hhex-VP16GR fusion construct suggested that endogenous hhex activity during gastrulation is essential for the formation of ventral pancreatic progenitor cells. These observations suggest that, beyond its role in liver development, hhex controls specification of a vpp1-positive endodermal cell population during gastrulation that is required for the formation of the ventral pancreas.
引用
收藏
页码:8594 / 8599
页数:6
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