Koyama E, Yamaai T, Iseki S, Ohuchi H, Nohno T, Yoshioka H, Hayashi Y, Leatherman J L, Golden E B, Noji S, Pacifici M
Department of Anatomy and Histology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Dev Dyn. 1996 May;206(1):59-72. doi: 10.1002/(SICI)1097-0177(199605)206:1<59::AID-AJA6>3.0.CO;2-#.
Tooth development involves reciprocal epithelial-mesenchymal interactions, polarized growth, mesenchyme condensation, and complex morphogenetic events. Because these processes bear similarities to those occurring in the developing limb, we asked whether morphogenetic signals found in the limb also occur in the developing tooth. We grafted mouse embryo tooth germs to the anterior margin of host chick embryo wing buds and determined whether the dental tissues had polarizing activity. Indeed, the grafts induced supernumerary digits. Activity of both molar and incisor tooth germs increased from bud to cap stages and was maximal at late bell stage in newborn. With further development the polarizing activity began to decrease, became undetectable in adult molar mesenchyme but persisted in incisor mesenchyme, correlating with the fact that incisors grow throughout postnatal life while molars do not. When different portions of neonatal incisors were assayed, a clear proximo-distal gradient of activity was apparent, with maximal activity restricted to the most proximal portion where undifferentiated mesenchyme and enamel organ reside. In situ hybridizations demonstrated that prior to induction of supernumerary digits, the tooth germ grafts induced expression in host tissue of Hoxd-12 and Hoxd-13. In addition, whole-mount in situ hybridizations and immunohistochemistry showed that developing tooth germs express Sonic hedgehog (Shh). Shh expression was first detected in bud stage tooth germs; at later stages Shh transcripts were prominent in enamel knot and differentiating ameloblasts at the cuspal region. We concluded that tooth germs possess polarizing activity and produce polarizing factors such as Shh. As in the limb, these factor(s) and activity probably play key roles in establishing polarity and regulating morphogenesis during early tooth development. Given its subsequent association with differentiating ameloblasts, Shh probably participates also in cytogenetic events during odontogenesis.
牙齿发育涉及上皮-间充质的相互作用、极化生长、间充质凝聚以及复杂的形态发生事件。由于这些过程与肢体发育中的过程相似，我们不禁要问，肢体中发现的形态发生信号是否也存在于发育中的牙齿中。我们将小鼠胚胎牙胚移植到宿主鸡胚胎翼芽的前缘，以确定牙齿组织是否具有极化活性。事实上，这些移植诱导了额外指（趾）的形成。磨牙和切牙牙胚的活性从蕾状期到帽状期逐渐增加，并在新生小鼠的晚期钟状期达到最大值。随着进一步发育，极化活性开始下降，在成年磨牙间充质中无法检测到，但在切牙间充质中持续存在，这与切牙在出生后整个生命过程中持续生长而磨牙则不然这一事实相关。当检测新生切牙的不同部分时，明显出现了从近端到远端的活性梯度，最大活性局限于未分化间充质和釉器所在的最近端部分。原位杂交表明，在诱导额外指（趾）形成之前，牙胚移植在宿主组织中诱导了Hoxd - 12和Hoxd - 13的表达。此外，整体原位杂交和免疫组织化学显示，发育中的牙胚表达音猬因子（Shh）。Shh表达首先在蕾状期牙胚中检测到；在后期阶段，Shh转录本在釉结和牙尖区域分化的成釉细胞中显著。我们得出结论，牙胚具有极化活性并产生诸如Shh等极化因子。与肢体一样，这些因子和活性可能在牙齿早期发育过程中建立极性和调节形态发生方面发挥关键作用。鉴于其随后与分化的成釉细胞相关联，Shh可能也参与了牙发生过程中的细胞遗传学事件。
