Krull Catherine E, Lansford Rusty, Gale Nicholas W, Collazo Andres, Marcelle Christophe, Yancopoulos George D, Fraser Scott E, Bronner-Fraser Marianne
Division of Biology and Beckman Institute, California Institute of Technology, Pasadena 91125, USA.
Curr Biol. 1997 Aug 1;7(8):571-80. doi: 10.1016/s0960-9822(06)00256-9.
In the trunk of avian embryos, neural crest migration through the somites is segmental, with neural crest cells entering the rostral half of each somitic sclerotome but avoiding the caudal half. Little is known about the molecular nature of the cues-intrinsic to the somites-that are responsible for this segmental migration of neural crest cells.
We demonstrate that Eph-related receptor tyrosine kinases and their ligands are essential for the segmental migration of avian trunk neural crest cells through the somites. EphB3 localizes to the rostral half-sclerotome, including the neural crest, and the ligand ephrin-B1 has a complementary pattern of expression in the caudal half-sclerotome. To test the functional significance of this striking asymmetry, soluble ligand ephrin-B1 was added to interfere with receptor function in either whole trunk explants or neural crest cells cultured on alternating stripes of ephrin-B1 versus fibronection. Neural crest cells in vitro avoided migrating on lanes of immobilized ephrin-B1; the addition of soluble ephrin-B1 blocked this inhibition. Similarly, in whole trunk explants, the metameric pattern of neural crest migration was disrupted by addition of soluble ephrin-B1, allowing entry of neural crest cells into caudal portions of the sclerotome.
Both in vivo and in vitro, the addition of soluble ephrin-B1 results in a loss of the metameric migratory pattern and a disorganization of neural crest cell movement. These results demonstrate that Eph-family receptor tyrosine kinases and their transmembrane ligands are involved in interactions between neural crest and sclerotomal cells, mediating an inhibitory activity necessary to constrain neural precursors to specific territories in the developing nervous system.
在鸟类胚胎的躯干中，神经嵴通过体节的迁移是分节的，神经嵴细胞进入每个体节性硬骨节的头侧半部分，但避开尾侧半部分。关于体节内在的、负责神经嵴细胞这种分节迁移的信号分子本质，人们了解甚少。
我们证明，Eph相关受体酪氨酸激酶及其配体对于鸟类躯干神经嵴细胞通过体节的分节迁移至关重要。EphB3定位于头侧半硬骨节，包括神经嵴，而配体ephrin-B1在尾侧半硬骨节中具有互补的表达模式。为了测试这种显著不对称性的功能意义，添加可溶性配体ephrin-B1以干扰整个躯干外植体或在ephrin-B1与纤连蛋白交替条纹上培养的神经嵴细胞中的受体功能。体外的神经嵴细胞避免在固定化ephrin-B1的条带上迁移；添加可溶性ephrin-B1可阻断这种抑制作用。同样，在整个躯干外植体中，添加可溶性ephrin-B1会破坏神经嵴迁移的节段模式，使神经嵴细胞能够进入硬骨节的尾侧部分。
无论在体内还是体外，添加可溶性ephrin-B1都会导致节段性迁移模式丧失和神经嵴细胞运动紊乱。这些结果表明，Eph家族受体酪氨酸激酶及其跨膜配体参与神经嵴与硬骨节细胞之间的相互作用，介导将神经前体细胞限制在发育中的神经系统特定区域所需的抑制活性。
