Qu Jian, Li Xiaofan, Novitch Bennet G, Zheng Ye, Kohn Matthew, Xie Jian-Ming, Kozinn Spencer, Bronson Roderick, Beg Amer A, Minden Audrey
Department of Biological Sciences, Columbia University, New York, New York 10025, USA.
Mol Cell Biol. 2003 Oct;23(20):7122-33. doi: 10.1128/MCB.23.20.7122-7133.2003.
The serine/threonine kinase PAK4 is a target for the Rho GTPase Cdc42 and has been shown to regulate cell morphology and cytoskeletal organization in mammalian cells. To examine the physiological and developmental functions of PAK4, we have disrupted the PAK4 gene in mice. The absence of PAK4 led to lethality by embryonic day 11.5, a result most likely due to a defect in the fetal heart. Striking abnormalities were also evident in the nervous systems of PAK4-deficient embryos. These embryos had dramatic defects in neuronal development and axonal outgrowth. In particular, spinal cord motor neurons and interneurons failed to differentiate and migrate to their proper positions. This is probably related to the role for PAK4 in the regulation of cytoskeletal organization and cell and/or extracellular matrix adhesion. PAK4-null embryos also had defects in proper folding of the caudal portion of the neural tube, suggesting an important role for PAK4 in neural tube development.
丝氨酸/苏氨酸激酶PAK4是Rho GTP酶Cdc42的作用靶点，并且已证明它在哺乳动物细胞中调节细胞形态和细胞骨架组织。为了研究PAK4的生理和发育功能，我们在小鼠中破坏了PAK4基因。PAK4的缺失导致胚胎在第11.5天死亡，这一结果很可能是由于胎儿心脏缺陷所致。在PAK4缺陷胚胎的神经系统中也明显存在显著异常。这些胚胎在神经元发育和轴突生长方面存在严重缺陷。特别是，脊髓运动神经元和中间神经元无法分化并迁移到其适当位置。这可能与PAK4在调节细胞骨架组织以及细胞和/或细胞外基质黏附中的作用有关。PAK4基因敲除胚胎在神经管尾部的正确折叠方面也存在缺陷，这表明PAK4在神经管发育中起重要作用。
