Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 78249, USA.
Dev Biol. 2012 Jan 1;361(1):125-36. doi: 10.1016/j.ydbio.2011.10.019. Epub 2011 Oct 20.
The interaction between the cranial neural crest (NC) and the epibranchial placode is critical for the formation of parasympathetic and visceral sensory ganglia, respectively. However, the molecular mechanism that controls this intercellular interaction is unknown. Here we show that the spatiotemporal expression of Fibroblast growth factor 8 (Fgf8) is strategically poised to control this cellular relationship. A global reduction of Fgf8 in hypomorph embryos leads to an early loss of placode-derived sensory ganglia and reduced number of NC-derived postganglionic (PG) neurons. The latter finding is associated with the early loss of NC cells by apoptosis. This loss occurs concurrent with the interaction between the NC and placode-derived ganglia. Conditional knockout of Fgf8 in the anterior mesoderm shows that this tissue source of Fgf8 has a specific influence on the formation of PG neurons. Unlike the global reduction of Fgf8, mesodermal loss of Fgf8 leads to a deficiency in PG neurons that is independent of NC apoptosis or defects in placode-derived ganglia. We further examined the differentiation of PG precursors by using a quantitative approach to measure the intensity of Phox2b, a PG neuronal determinant. We found reduced numbers and immature state of PG precursors emerging from the placode-derived ganglia en route to their terminal target areas. Our findings support the view that global expression of Fgf8 is required for early NC survival and differentiation of placode-derived sensory neurons, and reveal a novel role for mesodermal Fgf8 on the early differentiation of the NC along the parasympathetic PG lineage.
颅神经嵴（NC）和脑颅前神经褶之间的相互作用对于副交感神经和内脏感觉神经节的形成分别是至关重要的。然而，控制这种细胞间相互作用的分子机制尚不清楚。在这里，我们显示成纤维细胞生长因子 8（Fgf8）的时空表达被战略性地置于控制这种细胞关系的位置。在低等位基因胚胎中 Fgf8 的全局减少导致脑颅前神经褶衍生的感觉神经节的早期丢失和 NC 衍生的节后（PG）神经元数量减少。后一种发现与 NC 细胞通过细胞凋亡的早期丢失有关。这种丢失发生在 NC 和脑颅前神经褶衍生的神经节之间的相互作用过程中。Fgf8 在头侧中胚层中的条件性敲除显示该组织来源的 Fgf8 对 PG 神经元的形成具有特异性影响。与 Fgf8 的全局减少不同，中胚层缺失 Fgf8 导致 PG 神经元的缺乏，这与 NC 凋亡或脑颅前神经褶衍生的神经节的缺陷无关。我们进一步通过使用定量方法来测量 PG 神经元决定因子 Phox2b 的强度来检查 PG 前体的分化。我们发现从脑颅前神经褶衍生的神经节中出现的 PG 前体数量减少并且处于不成熟状态，这是其向终末靶区迁移的过程。我们的发现支持这样一种观点，即 Fgf8 的全局表达对于 NC 的早期存活和脑颅前神经褶衍生的感觉神经元的分化是必需的，并揭示了中胚层 Fgf8 在 NC 沿着副交感 PG 谱系的早期分化中的新作用。
