Yoshizato Katsutoshi
Department of Biological Science, Graduate School of Science, Hiroshima University, Higashihiroshima, 739-8526, Japan.
Int Rev Cytol. 2007;260:213-60. doi: 10.1016/S0074-7696(06)60005-3.
The epidermis of an anuran larva is composed of apical and skein cells that are both mitotically active and self-renewed through larval life. In contrast, the epidermis of an adult frog, with typical stratified squamous epithelium composed of germinative basal, spinous, granular, and cornified cells, is histologically identical to the mammalian epidermis. Two important issues have not yet been addressed in the study of the development of anuran skin. One is the origin of adult basal cells in the larval epidermis and the other is the mechanism by which larval basal cells are transformed into adult basal cells in a region- (body- and tail-) dependent manner. The cell lineage relationship between the larval and adult epidermal cells was determined by examining the expression profiles of several genes that are expressed specifically in larval and/or adult epidermal cells and differentiation profiles of larval basal cells cultured in the presence of thyroid hormone (TH). Histological analyses using several markers led to the identification of the skin transformation center (STC) where the conversion of larval skin to the adult counterpart is taking place. The STC emerges at a specific place in the body skin and at a specific stage of larval development. The STC progressively "moves" into and "invades" the adjacent larval region of the trunk skin as a larva develops, converting the larval skin into the preadult skin, but never into the tail region. The larva to preadult skin conversion requires an epidermal-mesenchymal interaction. The genesis of preadult basal cells is suppressed in the tail epidermis due to the influence of underlying mesenchyme in the tail region. PDGF signaling is one of the molecular cues of epidermal-mesenchymal interactions. In addition, a unique feature of anuran skin metamorphosis is presented referring to the skin of other vertebrates. Histological comparisons of the skin among vertebrate species strongly suggested a similarity between the anuran larval skin and the teleost fish adult skin and between the anuran adult skin and the adult skin of other tetrapod species. Based on these similarities, the evolutional significance of anuran skin metamorphosis is proposed. Finally, studies are reviewed that reveal the molecular mechanism of anuran metamorphosis in relation to TH-TR-TRE signaling. The results of these studies suggest new aspects of the biological significance of TH, and also enable us to envision concerted regulations of the expression of a gene in the frame of the gene network responsible for metamorphic remodeling of larval tissues. The present review will contribute to an understanding of the molecular mechanism of region-dependent skin development of anurans from not only a metamorphic but also from an evolutional point of view, and will provide a new way to understand the biological significance of TH in anurans.
无尾两栖类幼体的表皮由顶端细胞和丝状细胞组成，这些细胞在幼体期均具有有丝分裂活性且能自我更新。相比之下，成年蛙的表皮具有典型的复层鳞状上皮，由生发层基底细胞、棘细胞、颗粒细胞和角质化细胞组成，在组织学上与哺乳动物的表皮相同。在无尾两栖类皮肤发育的研究中，有两个重要问题尚未得到解决。一个是成年基底细胞在幼体表皮中的起源，另一个是幼体基底细胞以区域（身体和尾部）依赖的方式转化为成年基底细胞的机制。通过检测在幼体和/或成年表皮细胞中特异性表达的几种基因的表达谱以及在甲状腺激素（TH）存在下培养的幼体基底细胞的分化谱，确定了幼体和成年表皮细胞之间的细胞谱系关系。使用几种标记物进行的组织学分析导致了皮肤转化中心（STC）的鉴定，在该中心幼体皮肤正在转化为成年皮肤。STC出现在身体皮肤的特定位置和幼体发育的特定阶段。随着幼体的发育，STC逐渐“移动”并“侵入”躯干皮肤相邻的幼体区域，将幼体皮肤转化为成年前皮肤，但从未进入尾部区域。幼体到成年前皮肤的转化需要表皮 - 间充质相互作用。由于尾部区域潜在间充质的影响，成年前基底细胞的发生在尾部表皮中受到抑制。血小板衍生生长因子（PDGF）信号传导是表皮 - 间充质相互作用的分子线索之一。此外，参照其他脊椎动物的皮肤，呈现了无尾两栖类皮肤变态的一个独特特征。脊椎动物物种之间皮肤的组织学比较强烈表明，无尾两栖类幼体皮肤与硬骨鱼成年皮肤之间以及无尾两栖类成年皮肤与其他四足动物物种的成年皮肤之间存在相似性。基于这些相似性，提出了无尾两栖类皮肤变态的进化意义。最后，综述了揭示与TH - TR - TRE信号传导相关的无尾两栖类变态分子机制的研究。这些研究结果揭示了TH生物学意义的新方面，也使我们能够设想在负责幼体组织变态重塑的基因网络框架内基因表达的协同调控。本综述将有助于从变态和进化的角度理解无尾两栖类区域依赖性皮肤发育的分子机制，并将提供一种新的方式来理解TH在无尾两栖类中的生物学意义。
