Inoue T, Chisaka O, Matsunami H, Takeichi M
Department of Biophysics, Faculty of Science, Kyoto University, Japan.
Dev Biol. 1997 Mar 15;183(2):183-94. doi: 10.1006/dbio.1996.8501.
Mammalian cadherin-6 (K-cadherin, cad6) was originally identified by means of the polymerase chain reaction, but its biological functions have not yet been determined. We analyzed the expression pattern of the mouse homologue of this cadherin during development and found that it was transiently expressed in restricted rhombomeres and in other subdivisions of the neural plate and tube. In the midbrain and anterior hindbrain of E8.0-8.5 embryos, cad6 was expressed only in neural crest-generating regions. In contrast, in the posterior hindbrain and contiguous spinal cord of these embryos, cad6 occurred throughout the neural plate, forming a sharp anterior limit at the future rhombomere 4 and 5 boundary. Subsequently, this neural plate expression became confined to rhombomere 6, although most of the neural crest-generating areas remained positive throughout the body. Neural crest cells expressing cad6 migrated out of the neural tube, and subsequently accumulated mainly along peripheral nerves. We then studied the effect of Hoxa-1 mutation on the expression of cad6, as their expressions spatiotemporally overlapped with each other in the early posterior hindbrain. In E8.0-8.5 Hoxa-1 mutants, cad6 expression was suppressed in the region of rhombomeres 4 to 6, although that in the other regions was not essentially affected. At later stages, however, cad6-positive crest cells appeared and migrated out of rhombomeres 4 to 6, indicating that the suppression of cad6 expression was transient and restricted to early stages. Importantly, this effect of the Hoxa-1 mutation concurred with the timing of the expression of this gene. We also studied Hoxa-3 mutants, but found no effect of this mutation on the cad6 expression pattern. These findings suggest that cad6 may contribute to the formation of the segmental structure of the early brain through its ability to confer specific adhesiveness on cells and that Hoxa-1 may be required for early cad6 expression in the posterior hindbrain.
哺乳动物钙黏蛋白-6（K-钙黏蛋白，cad6）最初是通过聚合酶链反应鉴定出来的，但其生物学功能尚未确定。我们分析了该钙黏蛋白小鼠同源物在发育过程中的表达模式，发现它在特定的菱脑节以及神经板和神经管的其他亚区域中短暂表达。在E8.0 - 8.5胚胎的中脑和前脑后部，cad6仅在神经嵴产生区域表达。相反，在这些胚胎的后脑后部和相邻脊髓中，cad6在整个神经板中都有表达，在未来的菱脑节4和5边界处形成一个明显的前部界限。随后，这种神经板表达局限于菱脑节6，尽管大多数神经嵴产生区域在全身仍呈阳性。表达cad6的神经嵴细胞从神经管迁移出来，随后主要沿着外周神经聚集。然后我们研究了Hoxa - 1突变对cad6表达的影响，因为它们在早期后脑后部的表达在时空上相互重叠。在E8.0 - 8.5的Hoxa - 1突变体中，cad6在菱脑节4至6区域的表达受到抑制，尽管其他区域的表达基本未受影响。然而，在后期阶段，cad6阳性的嵴细胞出现并从菱脑节4至6迁移出来，这表明cad6表达的抑制是短暂的且仅限于早期阶段。重要的是，Hoxa - 1突变的这种影响与该基因的表达时间一致。我们还研究了Hoxa - 3突变体，但发现这种突变对cad6表达模式没有影响。这些发现表明，cad6可能通过赋予细胞特定黏附性的能力，对早期脑的节段结构形成做出贡献，并且Hoxa - 1可能是后脑后部cad6早期表达所必需的。
