Orioli D, Henkemeyer M, Lemke G, Klein R, Pawson T
European Molecular Biology Laboratory, Heidelberg, Germany.
EMBO J. 1996 Nov 15;15(22):6035-49.
Sek4 and Nuk are members of the Eph-related family of receptor protein-tyrosine kinases. These receptors interact with a set of cell surface ligands that have recently been implicated in axon guidance and fasciculation. We now demonstrate that the formation of the corpus callosum and anterior commissure, two major commissural axon tracts that connect the two cerebral hemispheres, is critically dependent on Sek4 and Nuk. While mice deficient in Nuk exhibit defects in pathfinding of anterior commissure axons, sek4 mutants have defects in corpus callosum formation. The phenotype in both axon tracts is markedly more severe in sek4/nuk1 double mutants, indicating that the two receptors act in a partially redundant fashion. sek4/nuk1 double mutants also exhibit specific guidance and fasciculation defects of diencephalic axon tracts. Moreover, while mice singly deficient in either Sek4 or Nuk are viable, most sek4/nuk1 double mutants die immediately after birth primarily due to a cleft palate. These results demonstrate essential and cooperative functions for Sek4 and Nuk in establishing axon pathways in the developing brain, and during the development of facial structures.
Sek4和Nuk是受体蛋白酪氨酸激酶Eph相关家族的成员。这些受体与一组最近被认为与轴突导向和束状化有关的细胞表面配体相互作用。我们现在证明，胼胝体和前连合这两条连接两个大脑半球的主要连合轴突束的形成，严重依赖于Sek4和Nuk。虽然缺乏Nuk的小鼠在前连合轴突的路径寻找上表现出缺陷，但sek4突变体在胼胝体形成上存在缺陷。在sek4/nuk1双突变体中，这两条轴突束的表型明显更严重，表明这两种受体以部分冗余的方式发挥作用。sek4/nuk1双突变体还表现出间脑轴突束的特定导向和束状化缺陷。此外，虽然单独缺乏Sek4或Nuk的小鼠是存活的，但大多数sek4/nuk1双突变体在出生后立即死亡，主要是由于腭裂。这些结果证明了Sek4和Nuk在发育中的大脑中建立轴突通路以及面部结构发育过程中具有重要的协同功能。
