Cyclopamine and jervine in embryonic rat tongue cultures demonstrate a role for Shh signaling in taste papilla development and patterning: fungiform papillae double in number and form in novel locations in dorsal lingual epithelium
Cyclopamine and jervine in embryonic rat tongue cultures demonstrate a role for Shh signaling in taste papilla development and patterning: fungiform papillae double in number and form in novel locations in dorsal lingual epithelium
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DOI：
10.1016/s0012-1606(02)00014-3
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发表时间：
2003-02-01
影响因子：
2.7
通讯作者：
MacCallum, DK
中科院分区：
文献类型：
--
作者：
Mistretta, CM;Liu, HX;MacCallum, DK
从胚胎发育开始，哺乳动物舌头上的味觉乳头类型就具有固定的舌头前后位置。此外，在前舌上，真菌状乳头呈排状。在许多调节乳头位置和模式的潜在分子中，Sonic hedgehog （Shh）已经定位于早期舌头和发育中的乳头。我们使用胚胎、舌头器官培养系统，该系统保留了体内味觉乳头形态发生和模式的时间、空间和分子特征，以研究Shh在味觉乳头发育中的作用。将妊娠第14天的大鼠舌背乳头刚开始出现时的胚胎在器官培养中保存2天。在标准培养基中加入类固醇生物碱、环巴胺和杰文，这些物质专门破坏Shh信号通路，或Shh阻断抗体。对照组包括单独在标准培养基中培养的舌头，并添加了茄碱，一种在结构上类似环巴胺的生物碱，但不会破坏Shh信号。在环巴胺、菊胺或阻断抗体的培养中，与在标准培养基或茄碱中的舌头相比，舌背真菌状乳头的数量增加了一倍，其分布基本上消除了乳头间区域。此外，真菌状乳头在口腔舌后部发育，就在单个环状乳头的前面和旁边，真菌状乳头通常不发育的区域。Shh蛋白存在于胚胎舌头的所有真菌状乳头中，以及用标准培养基或环巴胺培养的舌头中，并明显定位于乳头的基底膜区域。Ptc蛋白的分布与Shh相似，尽管免疫产物更分散。在环巴胺和耶文培养中，在咽或腹侧舌上或舌中线沟上没有出现真菌状乳头，也没有改变单个环形乳头的发育。结果表明Shh在真菌状乳头的诱导和形成中起着重要作用，并表明在真菌状和环形乳头的发育和数量的形态发生控制上存在差异。此外，一个以前未知的，广泛的能力舌背上皮形成真菌状乳头在前和后口腔舌。(C) 2003 Elsevier Science（美国）版权所有。
From time of embryonic emergence, the gustatory papilla types on the mammalian tongue have stereotypic anterior and posterior tongue locations. Furthermore, on anterior tongue, the fungiform papillae are patterned in rows. Among the many molecules that have potential roles in regulating papilla location and pattern, Sonic hedgehog (Shh) has been localized within early tongue and developing papillae. We used an embryonic, tongue organ culture system that retains temporal, spatial, and molecular characteristics of in vivo taste papilla morphogenesis and patterning to study the role of Shh in taste papilla development. Tongues from gestational day 14 rat embryos, when papillae are just beginning to emerge on dorsal tongue, were maintained in organ culture for 2 days. The steroidal alkaloids, cyclopamine and jervine, that specifically disrupt the Shh signaling pathway, or a Shh-blocking antibody were added to the standard culture medium. Controls included tongues cultured in the standard medium alone, and with addition of solanidine, an alkaloid that resembles cyclopamine structurally but that does not disrupt Shh signaling. In cultures with cyclopamine, jervine, or blocking antibody, fungiform papilla numbers doubled on the dorsal tongue with a distribution that essentially eliminated inter-papilla regions, compared with tongues in standard medium or solanidine. In addition, fungiform papillae developed on posterior oral tongue, just in front of and beside the single circumvallate papilla, regions where fungiform papillae do not typically develop. The Shh protein was in all fungiform papillae in embryonic tongues, and tongue cultures with standard medium or cyclopamine, and was conspicuously localized in the basement membrane region of the papillae. Ptc protein had a similar distribution to Shh, although the immunoproduct was more diffuse. Fungiform papillae did not develop on pharyngeal or ventral tongue in cyclopamine and jervine cultures, or in the tongue midline furrow, nor was development of the single circumvallate papilla altered. The results demonstrate a prominent role for Shh in fungiform papilla induction and patterning and indicate differences in morphogenetic control of fungiform and circumvallate papilla development and numbers. Furthermore, a previously unknown, broad competence of dorsal lingual epithelium to form fungiform papillae on both anterior and posterior oral tongue is revealed. (C) 2003 Elsevier Science (USA). All rights reserved.