Zhang Y, Zhao X, Hu Y, St Amand T, Zhang M, Ramamurthy R, Qiu M, Chen Y
Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana 70118, USA.
Dev Dyn. 1999 May;215(1):45-53. doi: 10.1002/(SICI)1097-0177(199905)215:1<45::AID-DVDY5>3.0.CO;2-5.
We have used the mouse developing tooth germ as a model system to explore the transmission of Sonic hedgehog (Shh) signal in the induction of Patched (Ptc). In the early developing molar tooth germ, Shh is expressed in the dental epithelium, and the transcripts of Shh downstream target genes Ptc and Gli1 are expressed in dental epithelium as well as adjacent mesenchymal tissue. The homeobox gene Msx1 is also expressed in the dental mesenchyme of the molar tooth germ at this time. We show here that the expression of Ptc, but not Gli1, was downregulated in the dental mesenchyme of Msx1 mutants. In wild-type E11.0 molar tooth mesenchyme SHH-soaked beads induced the expression of Ptc and Gli1. However, in Msx1 mutant dental mesenchyme SHH-soaked beads were able to induce Gli1 but failed to induce Ptc expression, indicating a requirement for Msx1 in the induction of Ptc by SHH. Moreover, we show that another signaling molecule, BMP4, was able to induce Ptc expression in wild-type dental mesenchyme, but induced a distinct expression pattern of Ptc in the Msx1 mutant molar mesenchyme. We conclude that in the context of the tooth germ Msx1 is a component of the Shh signaling pathway that leads to Ptc induction. Our results also suggest that the precise pattern of Ptc expression in the prospective tooth-forming region is controlled and coordinated by at least two inductive signaling pathways.
我们已将小鼠发育中的牙胚作为模型系统，以探究 Sonic hedgehog（Shh）信号在诱导 Patched（Ptc）中的传递。在早期发育的磨牙牙胚中，Shh 在牙上皮中表达，Shh 下游靶基因 Ptc 和 Gli1 的转录本在牙上皮以及相邻的间充质组织中也有表达。此时，同源框基因 Msx1 也在磨牙牙胚的牙间充质中表达。我们在此表明，在 Msx1 突变体的牙间充质中，Ptc 的表达下调，而 Gli1 的表达未下调。在野生型 E11.0 磨牙牙间充质中，用 SHH 浸泡过的珠子可诱导 Ptc 和 Gli1 的表达。然而，在 Msx1 突变体的牙间充质中，用 SHH 浸泡过的珠子能够诱导 Gli1 的表达，但未能诱导 Ptc 的表达，这表明 SHH 诱导 Ptc 需要 Msx1。此外，我们还表明，另一种信号分子 BMP4 能够在野生型牙间充质中诱导 Ptc 的表达，但在 Msx1 突变体的磨牙间充质中诱导出了不同的 Ptc 表达模式。我们得出结论，在牙胚的背景下，Msx1 是导致 Ptc 诱导的 Shh 信号通路的一个组成部分。我们的结果还表明，在前牙形成区域中 Ptc 表达的精确模式是由至少两条诱导信号通路控制和协调的。
