Sonic hedgehog exerts distinct, stage-specific effects on tongue and taste papilla development
Sonic hedgehog exerts distinct, stage-specific effects on tongue and taste papilla development
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DOI：
10.1016/j.ydbio.2004.07.042
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发表时间：
2004-12-15
影响因子：
2.7
通讯作者：
Mistretta, CM
中科院分区：
文献类型：
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作者：
Liu, HX;MacCallum, DK;Mistretta, CM
味觉乳头是外胚层的特化，用来安置和分布味蕾及其更新细胞群在舌头上的特定位置。我们先前的研究表明，Sonic hedgehog(Shh)在胎鼠前乳头形成的特定时期，对胎鼠舌部菌状味觉乳头的数量和空间格局具有重要的调节作用。现在我们已经对Shh蛋白和补丁受体蛋白(PTC)进行了免疫定位，并测试了Shh在舌的形成、乳头安慰剂的出现、乳头数量和大小的发育以及形态发生后乳头的维持中的潜在作用。研究对象为妊娠12~18天[妊娠或胚胎(E)12~E18]的完整胚胎下颌骨或舌体，其中舌体和乳头体的发育具有天然的空间、时间和分子特征。加入环多巴胺、杰尔文或5E1阻断抗体后，Shh信号通路被破坏。Shh和PTC蛋白弥漫在舌前组织和早期舌肿中，并逐渐局限于乳头胎盘，然后局限于发育中的乳头区域。PTC在不同时期环绕乳头内致密的Shh免疫产物。当在培养的E12下颌骨中Shh信号被破坏时，舌头的形成被完全阻止。在舌培养启动的后期，Shh信号干扰改变了舌形的发育(E13)，并导致重新形成的菌状乳头分布，不符合正常的无乳头舌区(E13-EI4)。仅仅几个小时的Shh信号干扰就可以不可逆转地改变舌前部菌状乳头的数量和位置，并诱导磨牙间隆起上的乳头形成。然而，一旦乳头形成良好(E16-E18)，Shh显然在维持乳头方面没有明显的作用，舌头也没有保留在非典型位置增加真菌样乳头的能力。我们的数据不仅为Shh在舌和菌状乳头形成中的诱导和形态发生作用提供了证据，也表明Shh在维持乳头间隙和无乳头的舌区中发挥着作用。我们提出了Shh在高浓度时形成和维持乳头的模型，以及在低浓度时激活乳头间基因以维持无乳头上皮的模型。(C)2004 Elsevier Inc.保留所有权利。
Taste papillae are ectodermal specializations that serve to house and distribute the taste buds and their renewing cell populations in specific locations on the tongue. We previously showed that Sonic hedgehog (Shh) has a major role in regulating the number and spatial pattern of fungiform taste papillae on embryonic rat tongue, during a specific period of papilla formation from the prepapilla placode. Now we have immunolocalized the Shh protein and the Patched receptor protein (Ptc), and have tested potential roles for Shh in formation of the tongue, emergence of papilla placodes, development of papilla number and size, and maintenance of papillae after morphogenesis is advanced. Cultures of entire embryonic mandible or tongues from gestational days 12 to 18 [gestational or embryonic days (E)12-E18] were used, in which tongues and papillae develop with native spatial, temporal, and molecular characteristics. The Shh signaling pathway was disrupted with addition of cyclopamine, jervine, or the 5E1 blocking antibody. Shh and Ptc proteins are diffuse in prelingual tissue and early tongue swellings, and are progressively restricted to papilla placodes and then to regions of developing papillae. Ptc encircles the dense Shh immunoproduct in papillae at various stages. When the Shh signal is disrupted in cultures of E12 mandible, tongue formation is completely prevented. At later stages of tongue culture initiation, Shh signal disruption alters development of tongue shape (E13) and results in a repatterned fungiform papilla distribution that does not respect normally papilla-free tongue regions (E13-EI4). Only a few hours of Shh signal disruption can irreversibly alter number and location of fungiform papillae on anterior tongue and elicit papilla formation on the intermolar eminence. However, once papillae are well formed (E16-E18), Shh apparently does not have a clear role in papilla maintenance, nor does the tongue retain competency to add fungiform papillae in atypical locations. Our data not only provide evidence for inductive and morphogenetic roles for Shh in tongue and fungiform papilla formation, but also suggest that Shh functions to maintain the interpapilla space and papilla-free lingual regions. We propose a model for Shh function at high concentration to form and maintain papillae and, at low concentration, to activate between-papilla genes that maintain a papilla-free epithelium. (C) 2004 Elsevier Inc. All rights reserved.