Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis
Fgf3 signaling from the ventral diencephalon is required for early specification and subsequent survival of the zebrafish adenohypophysis
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DOI：
10.1242/dev.01235
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发表时间：
2004-08-01
期刊：
影响因子：
4.6
通讯作者：
Hammerschmidt, M
中科院分区：
文献类型：
--
作者：
Herzog, W;Sonntag, C;Hammerschmidt, M
脑下垂体由两个主要部分组成：神经起源的神经垂体和非神经外胚层起源的腺垂体。腺垂体的发育是由漏斗的信号蛋白控制的，漏斗是间脑的腹侧结构，形成神经垂体。在小鼠中，成纤维细胞生长因子Fgf8、Fgf10和Fgf18被认为影响垂体发育的多个过程：腺垂体原基的形态发生和图案化；以及腺垂体前体细胞的存活、增殖和分化特性。在这里，我们研究了Fgf3在斑马鱼脑下垂体发育过程中的作用，分析了lialfgf3缺失突变体。我们发现来自腹侧间脑的Fgf3信号是以一种非细胞自主的方式诱导潜在的腺垂体祖细胞中的lim3、Pit1和其他垂体特异性基因的表达。尽管没有这样的早期规范步骤，fgf3突变体继续形成一个独特的大小和形状正常的垂体腺，直到垂体腺。细胞因细胞凋亡而死亡。我们进一步证明，Sonic Hedgehog(Shh)不能挽救垂体发育，尽管它能够诱导Fgf3突变体的异位胎盘区的腺垂体细胞，这表明Fgf3不通过Shh发挥作用，Shh可以独立于Fgf3发挥作用。综上所述，我们的数据表明，Fgf3信号主要促进调控腺垂体前体细胞早期特定步骤的基因的转录激活。这种早期的特性似乎对随后的垂体细胞存活是必不可少的，但对垂体形态发生或垂体细胞增殖不是必需的。
The pituitary gland consists of two major parts: the neurohypophysis, which is of neural origin; and the adenobypophysis, which is of non-neural ectodermal origin. Development of the adenohypophysis is governed by signaling proteins from the infundibulum, a ventral structure of the diencephalon that gives rise to the neurohypophysis. In mouse, the fibroblast growth factors Fgf8, Fgf10 and Fgf18 are thought to affect multiple processes of pituitary development: morphogenesis and patterning of the adenohypophyseal anlage; and survival, proliferation and differential specification of adenohypophyseal progenitor cells. Here, we investigate the role of Fgf3 during pituitary development in the zebrafish, analyzing lialfgf3 null mutants. We show that Fgf3 signaling from the ventral diencephalon is required in a non-cell autonomous fashion to induce the expression of lim3, pit1 and other pituitary-specific genes in the underlying adenohypophyseal progenitor cells. Despite the absence of such early specification steps, fgf3 mutants continue to form a distinct pituitary anlage of normal size and shape, until adenohypophyseal. cells die by apoptosis. We further show that Sonic Hedgehog (Shh) cannot rescue pituitary development, although it is able to induce adenohypophyseal cells in ectopic placodal regions of fgf3 mutants, indicating that Fgf3 does not act via Shh, and that Shh can act independently of Fgf3. In sum, our data suggest that Fgf3 signaling primarily promotes the transcriptional activation of genes regulating early specification steps of adenohypophyseal progenitor cells. This early specification seems to be essential for the subsequent survival of pituitary cells, but not for pituitary morphogenesis or pituitary cell proliferation.