A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates fusion of primordia in the amniote face

A dynamic Shh expression pattern, regulated by SHH and BMP signaling, coordinates fusion of primordia in the amniote face
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DOI:
10.1242/dev.114835
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发表时间:
2015-02-01
期刊:
影响因子:
4.6
通讯作者:
Marcucio, Ralph S.
Marcucio, Ralph S.
中科院分区:
生物学2区
文献类型:
--
作者:
Hu, Diane;Young, Nathan M.;Marcucio, Ralph S.

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形态发生的机制还没有很好地理解,但在发育过程中塑造结构对于建立正确的生物体形式和功能至关重要。在这里,我们研究的机制,有助于塑造发展中国家的脸在面部原基融合的关键时期。这一发育时期是胚胎的面部表现出最大程度相似性的时期,这可能是由于融合发生以建立初级腭的必要性。我们的研究结果表明,分层诱导机制,包括迭代信号由音刺猬(SHH),然后骨形态发生蛋白(BMP),调节动态表达模式的Shh在外胚层覆盖额鼻(FNP)和上颌(MxP)的过程。此外,该Shh表达结构域有助于形态发生过程,其部分通过调节面部间充质中的细胞增殖来驱动FNP的球状突起朝向外侧鼻突和MxP的定向生长。我们发现的诱导机制的性质表明,面部原基的融合过程本质上是缓冲对产生适应不良的形态,如裂缝的主要腭,因为似乎有很少的机会发生变化,在扩展的Shh表达结构域的面部原基的外胚层。最终,这些结果可能解释了为什么这一时期的发展构成了一个典型的面部发展阶段之间的阿诺特。
The mechanisms of morphogenesis are not well understood, yet shaping structures during development is essential for establishing correct organismal form and function. Here, we examine mechanisms that help to shape the developing face during the crucial period of facial primordia fusion. This period of development is a time when the faces of amniote embryos exhibit the greatest degree of similarity, and it probably results from the necessity for fusion to occur to establish the primary palate. Our results show that hierarchical induction mechanisms, consisting of iterative signaling by Sonic hedgehog (SHH) followed by Bone morphogenetic proteins (BMPs), regulate a dynamic expression pattern of Shh in the ectoderm covering the frontonasal (FNP) and maxillary (MxP) processes. Furthermore, this Shh expression domain contributes to the morphogenetic processes that drive the directional growth of the globular process of the FNP toward the lateral nasal process and MxP, in part by regulating cell proliferation in the facial mesenchyme. The nature of the induction mechanism that we discovered suggests that the process of fusion of the facial primordia is intrinsically buffered against producing maladaptive morphologies, such as clefts of the primary palate, because there appears to be little opportunity for variation to occur during expansion of the Shh expression domain in the ectoderm of the facial primordia. Ultimately, these results might explain why this period of development constitutes a phylotypic stage of facial development among amniotes.