The LIM homeodomain transcription factors Lhx6 and Lhx7 are key regulators of mammalian dentition.
The LIM homeodomain transcription factors Lhx6 and Lhx7 are key regulators of mammalian dentition.
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DOI：
10.1016/j.ydbio.2009.07.001
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发表时间：
2009-09-15
影响因子：
2.7
通讯作者：
Pachnis, Vassilis
中科院分区：
文献类型：
--
作者：
Denaxa, Myrto;Sharpe, Paul T.;Pachnis, Vassilis
编码LIM同源结构域转录因子的基因与胚胎发生过程中的细胞类型规范和分化有关。Lhx6和Lhx7是该家族的两个密切相关的成员，它们在上颌和下颌突的外切间质中表达，并被认为控制第一鳃弓（BA1）的模式和牙形成。然而，单突变纯合的小鼠要么没有颅骨缺陷（Lhx6），要么只有腭裂（Lhx7）。为了揭示Lhx6和Lhx7在颅骨形态发生中的潜在冗余活性，我们产生了具有野生型和突变型等位基因组合的小鼠。双纯合子小鼠颅骨有特征性的缺陷，出生后不久就会死亡，很可能是因为腭裂。此外，Lhx6/7缺陷胚缺乏臼齿。双突变体中磨牙的缺失不是由于BA1的模式缺陷，而是由于磨牙间质的不规范。尽管臼齿发育不全，lhx6 /7缺陷的动物有正常的门牙，在上颌骨两侧有一对多余的门牙状牙齿。我们的实验表明，LIM同源结构域蛋白Lhx6和Lhx7的冗余活性对哺乳动物牙列的颅面发育和模式形成至关重要。
Genes encoding LIM homeodomain transcription factors are implicated in cell type specification and differentiation during embryogenesis. Two closely related members of this family, Lhx6 and Lhx7, are expressed in the ectomesenchyme of the maxillary and mandibular processes and have been suggested to control patterning of the first branchial arch (BA1) and odontogenesis. However, mice homozygous for single mutations either have no cranial defects (Lhx6) or show only cleft palate (Lhx7). To reveal the potential redundant activities of Lhx6 and Lhx7 in cranial morphogenesis, we generated mice with all combinations of wild-type and mutant alleles. Double homozygous mice have characteristic defects of the cranial skeleton and die shortly after birth, most likely because of cleft palate. In addition, Lhx6/7 deficient embryos lack molar teeth. The absence of molars in double mutants is not due to patterning defects of BA1 but results from failure of specification of the molar mesenchyme. Despite molar agenesis, Lhx6/7-deficient animals have normal incisors which, in the maxilla, are flanked by a supernumerary pair of incisor-like teeth. Our experiments demonstrate that the redundant activities of the LIM homeodomain proteins Lhx6 and Lhx7 are critical for craniofacial development and patterning of mammalian dentition.
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影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
3.4
作者：
Fragkouli, A;Hearn, C;Pachnis, V
通讯作者：
Pachnis, V
影响因子：
3
作者：
Courtney, JM;Blackburn, J;Sharpe, PT
通讯作者：
Sharpe, PT
影响因子：
2.6
作者：
Duprez, D;Bella, EJD;FrancisWest, PH
通讯作者：
FrancisWest, PH
在没有刺猬信号的情况下，头发发育异常和明显的卵泡转化向乳腺。
影响因子：
11.8
作者：
Gritli-Linde, Amel;Hallberg, Kristina;Harfe, Brian D.;Reyahi, Azadeh;Kannius-Janson, Marie;Nilsson, Jeanette;Cobourne, Martyn T.;Sharpe, Paul T.;McMahon, Andrew P.;Linde, Anders
通讯作者：
Linde, Anders