Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation
Sek4 and Nuk receptors cooperate in guidance of commissural axons and in palate formation
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DOI：
10.1002/j.1460-2075.1996.tb00992.x
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发表时间：
1996-11-15
期刊：
影响因子：
11.4
通讯作者：
Pawson, T
中科院分区：
文献类型：
--
作者：
Orioli, D;Henkemeyer, M;Pawson, T
Sek4和Nuk是ef相关受体蛋白酪氨酸激酶家族的成员。这些受体与一组细胞表面配体相互作用，这些配体最近被认为与轴突引导和束控有关。我们现在证明胼胝体和前连合（连接两个大脑半球的两个主要连合轴突束）的形成严重依赖于Sek4和Nuk。Nuk基因缺失的小鼠在前连合轴突的寻路上存在缺陷，而sek4突变的小鼠在胼胝体的形成上存在缺陷。在sek4/nuk(1)双突变体中，两个轴突束的表型明显更严重，表明这两个受体以部分冗余的方式起作用。Sek4 /nuk(1)双突变体也表现出间脑轴突束的特异性引导和束控缺陷。此外，虽然单个缺乏Sek4或Nuk的小鼠可以存活，但大多数Sek4 / Nuk(1)双突变体在出生后立即死亡，主要原因是腭裂。这些结果表明，Sek4和Nuk在发育中的大脑轴突通路的建立以及面部结构的发育过程中具有重要的协同作用。
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/nuk(1) double mutants, indicating that the two receptors act in a partially redundant fashion. sek4/nuk(1) 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/nuk(1) 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.