Hand transcription factors cooperatively regulate development of the distal midline mesenchyme
Hand transcription factors cooperatively regulate development of the distal midline mesenchyme
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DOI：
10.1016/j.ydbio.2007.07.036
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发表时间：
2007-10-01
影响因子：
2.7
通讯作者：
Yanagisawa, Hiromi
中科院分区：
文献类型：
--
作者：
Barbosa, Ana C.;Funato, Noriko;Yanagisawa, Hiromi
Hand蛋白是进化上保守的基本螺旋-环-螺旋（bHLH）转录因子，与神经嵴衍生组织、心脏和肢体的发育有关。Hand1在鳃弓的远端（腹侧）区表达，而Hand2表达域向腹侧延伸，占据下颌弓的三分之二。为了避免Hand1或Hand2缺失胚胎的早期胚胎致死性，并研究它们在神经嵴发育中的作用，我们培养了神经嵴特异性缺失Hand1和Hand2突变等位基因的各种组合的小鼠。单独切除神经嵴细胞中的Hand1并不影响胚胎发育，然而，进一步去除一个Hand2等位基因或删除Hand2腹外侧鳃裂弓的表达可能是由于远端中线间质生长受损导致了一种新的表型。虽然我们没有检测到野生型和Hand1/Hand2复合突变体在胚胎日(E)10.5时下颌远端弓的增殖或凋亡的变化，但在E12.5时，在远端间质中观察到Pax9， Msx2和Prx2的失调。此外，牙间间质和Meckel软骨远端联合发育不全，导致在发育不全的融合下颌骨内形成单一的融合下门牙。这些发现表明Hand转录因子在颅面和牙齿发育的转录回路中的重要性。(C) 2007爱思唯尔公司版权所有。
Hand proteins are evolutionally conserved basic helix-loop-helix (bHLH) transcription factors implicated in development of neural crest-derived tissues, heart and limb. Hand1 is expressed in the distal (ventral) zone of the branchial arches, whereas the Hand2 expression domain extends ventrolaterally to occupy two-thirds of the mandibular arch. To circumvent the early embryonic lethality of Hand1 or Hand2-null embryos and to examine their roles in neural crest development, we generated mice with neural crest-specific deletion of Hand1 and various combinations of mutant alleles of Hand2. Ablation of Hand1 alone in neural crest cells did not affect embryonic development, however, further removing one Hand2 allele or deleting the ventrolateral branchial arch expression of Hand2 led to a novel phenotype presumably due to impaired growth of the distal midline mesenchyme. Although we failed to detect changes in proliferation or apoptosis between the distal mandibular arch of wild-type and Hand1/Hand2 compound mutants at embryonic day (E)10.5, dysregulation of Pax9, Msx2 and Prx2 was observed in the distal mesenchyme at E12.5. In addition, the inter-dental mesenchyme and distal symphysis of Meckel's cartilage became hypoplastic, resulting in the formation of a single fused lower incisor within the hypoplastic fused mandible. These findings demonstrate the importance of Hand transcription factors in the transcriptional circuitry of craniofacial and tooth development. (C) 2007 Elsevier Inc. All rights reserved.