Lin John W, Biankin Andrew V, Horb Marko E, Ghosh Bidyut, Prasad Nijaguna B, Yee Nelson S, Pack Michael A, Leach Steven D
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Dev Biol. 2004 Oct 15;274(2):491-503. doi: 10.1016/j.ydbio.2004.07.001.
Mammalian studies have implicated important roles for the basic helix-loop-helix transcription factor Ptf1a-p48 in the development of both exocrine and endocrine pancreas. We have cloned the Ptf1a-p48 ortholog in Danio rerio. Early zebrafish ptf1a expression is observed in developing hindbrain and in endodermal pancreatic precursors. Analysis of ptf1a and insulin expression reveals a population of exocrine precursors that, throughout early development, are temporally and spatially segregated from endocrine elements. Morpholino-mediated knockdown of ptf1a confirms early divergence of these endocrine and exocrine lineages. Ptf1a morphants lack differentiated exocrine pancreas, but maintain normal differentiation and organization of the principal islet. In addition to the exocrine phenotype, ptf1a knockdown also reduces the prevalence of a small population of anterior endocrine cells normally found outside the principal islet. Together, these findings suggest the presence of distinct ptf1a-dependent and ptf1a-independent precursor populations in developing zebrafish pancreas.
哺乳动物研究表明，碱性螺旋-环-螺旋转录因子Ptf1a-p48在胰腺外分泌和内分泌发育中起重要作用。我们已在斑马鱼中克隆出Ptf1a-p48直系同源基因。在斑马鱼发育早期，可在后脑和内胚层胰腺前体细胞中观察到ptf1a的表达。对ptf1a和胰岛素表达的分析显示，在整个早期发育过程中，一群外分泌前体细胞在时间和空间上与内分泌细胞分隔开来。吗啡啉介导的ptf1a敲低证实了这些内分泌和外分泌谱系的早期分化。Ptf1a敲低的斑马鱼缺乏分化的外分泌胰腺，但主要胰岛的正常分化和组织结构得以维持。除了外分泌表型外，ptf1a敲低还降低了通常在主要胰岛外发现的一小群前内分泌细胞的比例。这些发现共同表明，在发育中的斑马鱼胰腺中存在不同的ptf1a依赖和ptf1a非依赖前体细胞群。
