Vázquez-Echeverría Citlali, Dominguez-Frutos Elena, Charnay Patrick, Schimmang Thomas, Pujades Cristina
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/ Dr. Aiguader 88, 08003 Barcelona, Spain.
Dev Biol. 2008 Oct 1;322(1):167-78. doi: 10.1016/j.ydbio.2008.07.025. Epub 2008 Jul 30.
The inner ear, the sensory organ responsible for hearing and balance, contains specialized sensory and non-sensory epithelia arranged in a highly complex three-dimensional structure. To achieve this complexity, a tight coordination between morphogenesis and cell fate specification is essential during otic development. Tissues surrounding the otic primordium, and more particularly the adjacent segmented hindbrain, have been implicated in specifying structures along the anteroposterior and dorsoventral axes of the inner ear. In this work we have first characterized the generation and axial specification of the otic neurogenic domain, and second, we have investigated the effects of the mutation of kreisler/MafB--a gene transiently expressed in rhombomeres 5 and 6 of the developing hindbrain--in early otic patterning and cell specification. We show that kr/kr embryos display an expansion of the otic neurogenic domain, due to defects in otic patterning. Although many reports have pointed to the role of FGF3 in otic regionalisation, we provide evidence that FGF3 is not sufficient to govern this process. Neither Krox20 nor Fgf3 mutant embryos, characterized by a downregulation or absence of Fgf3 in r5 and r6, display ectopic neuroblasts in the otic primordium. However, Fgf3-/-Fgf10-/- double mutants show a phenotype very similar to kr/kr embryos: they present ectopic neuroblasts along the AP and DV otic axes. Finally, partial rescue of the kr/kr phenotype is obtained when Fgf3 or Fgf10 are ectopically expressed in the hindbrain of kr/kr embryos. These results highlight the importance of hindbrain-derived signals in the regulation of otic neurogenesis.
内耳是负责听觉和平衡的感觉器官，包含以高度复杂的三维结构排列的特殊感觉上皮和非感觉上皮。为了实现这种复杂性，在耳发育过程中，形态发生和细胞命运特化之间的紧密协调至关重要。耳原基周围的组织，尤其是相邻的分节后脑，与内耳前后轴和背腹轴上结构的特化有关。在这项工作中，我们首先表征了耳神经源性区域的产生和轴向特化，其次，我们研究了kreisler/MafB基因（在发育中的后脑菱脑节5和6中短暂表达的基因）突变对早期耳模式形成和细胞特化的影响。我们发现kr/kr胚胎由于耳模式形成缺陷而表现出耳神经源性区域的扩张。尽管许多报告指出FGF3在耳区域化中的作用，但我们提供的证据表明FGF3不足以控制这一过程。以r5和r6中Fgf3下调或缺失为特征的Krox20或Fgf3突变胚胎，在内耳原基中均未显示异位神经母细胞。然而，Fgf3-/-Fgf10-/-双突变体表现出与kr/kr胚胎非常相似的表型：它们沿内耳的前后轴和背腹轴出现异位神经母细胞。最后，当Fgf3或Fgf10在kr/kr胚胎的后脑异位表达时，可部分挽救kr/kr表型。这些结果突出了后脑衍生信号在耳神经发生调控中的重要性。
