Kitazawa Taro, Minoux Maryline, Ducret Sebastien, Rijli Filippo M
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
INSERM UMR 1121, Faculté de Chirurgie Dentaire, Université de Strasbourg, 8 rue Sainte Elisabeth, 67 000 Strasbourg, France.
J Dev Biol. 2022 Jan 31;10(1):9. doi: 10.3390/jdb10010009.
Providing appropriate positional identity and patterning information to distinct rostrocaudal subpopulations of cranial neural crest cells (CNCCs) is central to vertebrate craniofacial morphogenesis. genes are not expressed in frontonasal and first pharyngeal arch (PA1) CNCCs, whereas a single gene, , is necessary to provide patterning information to second pharyngeal arch (PA2) CNCCs. In frog, chick and mouse embryos, ectopic expression of in -negative CNCCs induced hypoplastic phenotypes of CNCC derivatives of variable severity, associated or not with homeotic transformation of a subset of PA1 structures into a PA2-like identity. Whether these different morphological outcomes are directly related to distinct overexpression levels is unknown. To address this issue, we selectively induced overexpression in mouse CNCCs, using a panel of mouse lines expressing different ectopic expression levels, including a newly generated knocked-in mouse line. While ectopic expression at only 60% of its physiological levels was sufficient for pinna duplication, ectopic expression at 100% of its normal level was required for complete homeotic repatterning of a subset of PA1 skeletal elements into a duplicated set of PA2-like elements. On the other hand, ectopic overexpression at non-physiological levels (200% of normal levels) led to an almost complete loss of craniofacial skeletal structures. Moreover, ectopic overexpression in CNCCs, while also resulting in severe craniofacial defects, did not induce homeotic changes of PA1-derived CNCCs, indicating specificity in repatterning a subset of -negative CNCCs. These results reconcile some discrepancies in previously published experiments and indicate that distinct subpopulations of CNCCs are differentially sensitive to ectopic levels of expression.
为颅神经嵴细胞（CNCCs）不同的头尾亚群提供适当的位置身份和模式信息是脊椎动物颅面形态发生的核心。基因不在额鼻和第一咽弓（PA1）的CNCCs中表达，而单个基因对于向第二咽弓（PA2）的CNCCs提供模式信息是必需的。在青蛙、鸡和小鼠胚胎中，在阴性CNCCs中异位表达会诱导出不同严重程度的CNCC衍生物发育不全的表型，这与PA1结构的一个子集向PA2样身份的同源转化有关或无关。这些不同的形态学结果是否与不同的过表达水平直接相关尚不清楚。为了解决这个问题，我们使用一组表达不同异位表达水平的小鼠品系，包括新生成的敲入小鼠品系，在小鼠CNCCs中选择性地诱导过表达。虽然仅在其生理水平的60%时异位表达就足以使耳廓复制，但要使PA1骨骼元素的一个子集完全同源重编程为一组重复的PA2样元素，则需要在其正常水平的100%时异位表达。另一方面，在非生理水平（正常水平的200%）异位过表达会导致颅面骨骼结构几乎完全丧失。此外，在CNCCs中异位过表达虽然也会导致严重的颅面缺陷，但不会诱导PA1衍生的CNCCs发生同源变化，这表明在重编程一部分阴性CNCCs时具有特异性。这些结果调和了先前发表的实验中的一些差异，并表明CNCCs的不同亚群对异位表达水平的敏感性不同。
