Wright Tracy J, Mansour Suzanne L
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112-5330, USA.
Development. 2003 Aug;130(15):3379-90. doi: 10.1242/dev.00555.
The inner ear, which contains the sensory organs specialised for audition and balance, develops from an ectodermal placode adjacent to the developing hindbrain. Tissue grafting and recombination experiments suggest that placodal development is directed by signals arising from the underlying mesoderm and adjacent neurectoderm. In mice, Fgf3 is expressed in the neurectoderm prior to and concomitant with placode induction and otic vesicle formation, but its absence affects only the later stages of otic vesicle morphogenesis. We show here that mouse Fgf10 is expressed in the mesenchyme underlying the prospective otic placode. Embryos lacking both Fgf3 and Fgf10 fail to form otic vesicles and have aberrant patterns of otic marker gene expression, suggesting that FGF signals are required for otic placode induction and that these signals emanate from both the hindbrain and mesenchyme. These signals are likely to act directly on the ectoderm, as double mutant embryos showed normal patterns of gene expression in the hindbrain. Cell proliferation and survival were not markedly affected in double mutant embryos, suggesting that the major role of FGF signals in otic induction is to establish normal patterns of gene expression in the prospective placode. Finally, examination of embryos carrying three out of the four mutant Fgf alleles revealed intermediate phenotypes, suggesting a quantitative requirement for FGF signalling in otic vesicle formation.
内耳包含专门用于听觉和平衡的感觉器官，它由与发育中的后脑相邻的外胚层基板发育而来。组织移植和重组实验表明，基板的发育是由来自下方中胚层和相邻神经外胚层的信号引导的。在小鼠中，Fgf3在基板诱导和耳泡形成之前及过程中在神经外胚层中表达，但其缺失仅影响耳泡形态发生的后期阶段。我们在此表明，小鼠Fgf10在前庭耳基板下方的间充质中表达。同时缺乏Fgf3和Fgf10的胚胎无法形成耳泡，并且耳标记基因表达模式异常，这表明FGF信号是耳基板诱导所必需的，并且这些信号来自后脑和间充质。这些信号可能直接作用于外胚层，因为双突变胚胎在后脑显示出正常的基因表达模式。双突变胚胎中的细胞增殖和存活没有受到明显影响，这表明FGF信号在耳诱导中的主要作用是在前庭基板中建立正常的基因表达模式。最后，对携带四个突变Fgf等位基因中的三个的胚胎进行检查，发现了中间表型，这表明在耳泡形成中对FGF信号传导存在定量需求。
