Two endothelin 1 effectors, hand2 and bapx1, pattern ventral pharyngeal cartilage and the jaw joint
Two endothelin 1 effectors, hand2 and bapx1, pattern ventral pharyngeal cartilage and the jaw joint
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DOI：
10.1242/dev.00339
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发表时间：
2003-04-01
期刊：
影响因子：
4.6
通讯作者：
Kimmel, CB
中科院分区：
文献类型：
--
作者：
Miller, CT;Yelon, D;Kimmel, CB
一种保守的内皮素1信号通路在小鼠、小鸡和斑马鱼中形成颌骨和其他咽部骨骼元件。在斑马鱼中，内皮素1（edn1或吸盘）是形成幼鱼前咽弓腹软骨和关节所必需的。在这里，我们提出了两个edn 1下游目标，bHLH转录因子Hand2和同源框转录因子Bapx1，介导背腹（DV）图案在前咽弓的斑马鱼的遗传分析。首先，我们表明，edn 1表达细胞在第一（下颌骨）和第二（舌骨）咽弓原基，位于最腹侧和周围的Hand2表达细胞。接下来，我们表明，沿着DV轴的早期第一弓原基，bapx1的表达在一个中间域，后来标志着颌骨关节，这个表达式需要edn1功能。bapx1的功能是下颌关节、Meckel软骨的关节相关关节后突和关节后骨形成所必需的。chd和gdf 5的颌骨关节表达也需要bapx 1功能。与edn 1类似，hand 2是腹侧咽软骨形成所需的。然而，早期腹弓edn 1依赖的五个基因（dlx3，EphA3，gsc，msxe和msxb）的表达都存在于hand2突变体。此外，msxe和msxb在hand 2突变体腹弓中上调。稍晚些时候，edn 1依赖的腹侧第一弓表达结构域的gsc是缺乏在hand 2突变体，提供了一个共同的下游目标edn 1和hand 2。在hand 2突变体中，bapx1表达存在于关节区域，并向腹侧扩展。此外，eng2的表达，通常局限于第一拱背中胚层，扩大腹侧在hand2和edn1突变体。因此，腹侧咽的规格涉及抑制背和中间（联合区）的命运。总之，我们的研究结果揭示了两个关键的edn1效应器的模式脊椎动物的下巴：手2指定腹咽软骨的下颌和bapx1指定下颌关节。
A conserved endothelin 1 signaling pathway patterns the jaw and other pharyngeal skeletal elements in mice, chicks and zebrafish. In zebrafish, endothelin 1 (edn1 or sucker) is required for formation of ventral cartilages and joints in the anterior pharyngeal arches of young larvae. Here we present genetic analyses in the zebrafish of two edn1 downstream targets, the bHLH transcription factor Hand2 and the homeobox transcription factor Bapx1, that mediate dorsoventral (DV) patterning in the anterior pharyngeal arches.First we show that edn1-expressing cells in the first (mandibular) and second (hyoid) pharyngeal arch primordia, are located most ventrally and surrounded by hand2-expressing cells. Next we show that along the DV axis of the early first arch primordia, bapx1 is expressed in an intermediate domain, which later marks the jaw joint, and this expression requires edn1 function. bapx1 function is required for formation of the jaw joint, the joint-associated retroarticular process of Meckel's cartilage, and the retroarticular bone. Jaw joint expression of chd and gdf5 also requires bapx1 function.Similar to edn1, hand2 is required for ventral pharyngeal cartilage formation. However, the early ventral arch edn1-dependent expression of five genes (dlx3, EphA3, gsc, msxe and msxb) are all present in hand2 mutants. Further, msxe and msxb are upregulated in hand2 mutant ventral arches. Slightly later, an edn1-dependent ventral first arch expression domain of gsc is absent in hand2 mutants, providing a common downstream target of edn1 and hand2. In hand2 mutants, bapx1 expression is present at the joint region, and expanded ventrally. In addition, expression of eng2, normally restricted to first arch dorsal mesoderm, expands ventrally in hand2 and edn1 mutants. Thus, ventral pharyngeal specification involves repression of dorsal and intermediate (joint region) fates. Together our results reveal two critical edn1 effectors that pattern the vertebrate jaw: hand2 specifies ventral pharyngeal cartilage of the lower jaw and bapx1 specifies the jaw joint.