Multiple roles for Hedgehog signaling in zebrafish pituitary development.
Multiple roles for Hedgehog signaling in zebrafish pituitary development.
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DOI：
10.1016/s0012-1606(02)00027-1
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发表时间：
2003-02
影响因子：
2.7
通讯作者：
Jennifer L Sbrogna;M. Barresi;R. Karlstrom
中科院分区：
文献类型：
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作者：
Jennifer L Sbrogna;M. Barresi;R. Karlstrom
脑下垂体或腺垂体的内分泌叶由神经板前缘的细胞通过涉及刺猬（Hh）、成纤维细胞生长因子（FGF）和骨形态发生蛋白（BMP）家族的分泌形态发生素的诱导相互作用形成。为了更好地了解Hh信号何时何地影响垂体发育，我们分析了阻断Hh信号的影响，包括阻断Hh信号（环巴胺治疗）和遗传（斑马鱼Hh通路突变体）。虽然目前的模型状态，Shh信号从口腔外胚层模式的垂体基板诱导后，我们的数据表明，Shh起着直接的早期作用，垂体诱导和图案，早期Hh信号来自相邻的神经外胚层。我们报告说，Hh信号是必要的10和15小时之间的发展诱导的斑马鱼腺垂体，一个时间时，SHH只在神经组织中表达。我们发现，Hh反应基因ptc 1和nk2.2在preplacodal细胞在神经管的前缘在这个时候表达，表明这些细胞直接接收Hh信号。随后（15-20小时）环巴胺治疗破坏nk2.2和催乳素的前表达，表明早期功能模式需要Hh信号。与Hh信号在垂体诱导和模式化中的直接作用一致，Shh的过表达导致Lim 3的腺垂体表达扩大，nk2.2扩展到后腺垂体，以及催乳素和生长激素分泌细胞的增加。我们还使用斑马鱼Hh通路突变体来记录当Hh信号通路的不同元件突变时发生的垂体缺陷的范围。这些缺陷，从腺垂体的完全丧失（smu/smo和yot/gli 2突变体）到更微妙的图案缺陷（dtr/gli 1突变体），可能与前脑无裂畸形和其他先天性疾病中观察到的人类Hh信号突变表型相关。我们的研究结果揭示了Hh信号在脊椎动物脑垂体形成中的多重和不同的作用，并表明Hh信号从神经外胚层是必要的诱导和功能模式的脊椎动物脑垂体。
The endocrine-secreting lobe of the pituitary gland, or adenohypophysis, forms from cells at the anterior margin of the neural plate through inductive interactions involving secreted morphogens of the Hedgehog (Hh), fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) families. To better understand when and where Hh signaling influences pituitary development, we have analyzed the effects of blocking Hh signaling both pharmacologically (cyclopamine treatments) and genetically (zebrafish Hh pathway mutants). While current models state that Shh signaling from the oral ectoderm patterns the pituitary after placode induction, our data suggest that Shh plays a direct early role in both pituitary induction and patterning, and that early Hh signals comes from adjacent neural ectoderm. We report that Hh signaling is necessary between 10 and 15 h of development for induction of the zebrafish adenohypophysis, a time when shh is expressed only in neural tissue. We show that the Hh responsive genes ptc1 and nk2.2 are expressed in preplacodal cells at the anterior margin of the neural tube at this time, indicating that these cells are directly receiving Hh signals. Later (15–20 h) cyclopamine treatments disrupt anterior expression of nk2.2 and Prolactin, showing that early functional patterning requires Hh signals. Consistent with a direct role for Hh signaling in pituitary induction and patterning, overexpression of Shh results in expanded adenohypophyseal expression of lim3, expansion of nk2.2 into the posterior adenohypophysis, and an increase in Prolactin- and Somatolactin-secreting cells. We also use the zebrafish Hh pathway mutants to document the range of pituitary defects that occur when different elements of the Hh signaling pathway are mutated. These defects, ranging from a complete loss of the adenohypophysis (smu/smo and yot/gli2 mutants) to more subtle patterning defects (dtr/gli1 mutants), may correlate to human Hh signaling mutant phenotypes seen in Holoprosencephaly and other congenital disorders. Our results reveal multiple and distinct roles for Hh signaling in the formation of the vertebrate pituitary gland, and suggest that Hh signaling from neural ectoderm is necessary for induction and functional patterning of the vertebrate pituitary gland.