Xu Q, Mellitzer G, Robinson V, Wilkinson D G
Division of Developmental Neurobiology, National Institute for Medical Research, London, UK.
Nature. 1999 May 20;399(6733):267-71. doi: 10.1038/20452.
The restriction of intermingling between specific cell populations is crucial for the maintenance of organized patterns during development. A striking example is the restriction of cell mixing between segments in the insect epidermis and the vertebrate hindbrain that may enable each segment to maintain a distinct identity. In the hindbrain, this is a result of different adhesive properties of odd- and even-numbered segments (rhombomeres), but an adhesion molecule with alternating segmental expression has not been found. However, blocking experiments suggest that Eph-receptor tyrosine kinases may be required for the segmental restriction of cells. Eph receptors and their membrane-bound ligands, ephrins, are expressed in complementary rhombomeres and, by analogy with their roles in axon pathfinding, could mediate cell repulsion at boundaries. Remarkably, transmembrane ephrins can themselves transduce signals, raising the possibility that bi-directional signalling occurs between adjacent ephrin- and Eph-receptor-expressing cells. We report here that mosaic activation of Eph receptors leads to sorting of cells to boundaries in odd-numbered rhombomeres, whereas mosaic activation of ephrins results in sorting to boundaries in even-numbered rhombomeres. These data implicate Eph receptors and ephrins in the segmental restriction of cell intermingling.
特定细胞群体之间的相互混合限制对于发育过程中组织结构模式的维持至关重要。一个显著的例子是昆虫表皮和脊椎动物后脑节段之间的细胞混合限制，这可能使每个节段保持独特的身份。在后脑中，这是奇数和偶数节段（菱脑节）具有不同黏附特性的结果，但尚未发现具有交替节段表达的黏附分子。然而，阻断实验表明Eph受体酪氨酸激酶可能是细胞节段限制所必需的。Eph受体及其膜结合配体ephrin在互补的菱脑节中表达，并且类似于它们在轴突导向中的作用，可能在边界处介导细胞排斥。值得注意的是，跨膜ephrin自身可以转导信号，这增加了在相邻表达ephrin和Eph受体的细胞之间发生双向信号传导的可能性。我们在此报告，Eph受体的镶嵌激活导致细胞在奇数菱脑节中向边界分选，而ephrin的镶嵌激活导致细胞在偶数菱脑节中向边界分选。这些数据表明Eph受体和ephrin参与了细胞混合的节段限制。
