Odemis Veysel, Lamp Elke, Pezeshki Gita, Moepps Barbara, Schilling Karl, Gierschik Peter, Littman Dan R, Engele Jürgen
Institute of Anatomy, University of Leipzig, Medical Faculty, Liebigstr. 13, 04103 Leipzig, Germany.
Mol Cell Neurosci. 2005 Dec;30(4):494-505. doi: 10.1016/j.mcn.2005.07.019. Epub 2005 Sep 29.
The chemokine CXCL12/SDF-1 and its receptor CXCR4 regulate the development and the function of the hematopoietic system and control morphogenesis of distinct brain areas. Here, we demonstrate that inactivation of CXCR4 results in a massive loss of spinal cord motoneurons and dorsal root ganglion neurons and, subsequently, in a reduced innervation of the developing mouse fore- and hindlimbs. However, only the death of sensory neurons seems to be a direct consequence of receptor inactivation as suggested by the observations that DRG neurons, but not motoneurons, of wild-type animals express CXCR4 and respond to CXCL12 with an increase in cell survival. In contrast, the increased death of motoneurons in CXCR4-deficient animals seems to result from impaired limb myogenesis and a subsequent loss of muscle-derived neurotrophic support. In summary, our findings unravel a previously unrecognized complex role of CXCL12/CXCR4 in the control of limb neuromuscular development.
趋化因子CXCL12/SDF-1及其受体CXCR4调节造血系统的发育和功能，并控制不同脑区的形态发生。在此，我们证明CXCR4失活会导致脊髓运动神经元和背根神经节神经元大量缺失，随后导致发育中的小鼠前肢和后肢的神经支配减少。然而，如野生型动物的背根神经节神经元而非运动神经元表达CXCR4并对CXCL12产生反应从而增加细胞存活这一观察结果所示，只有感觉神经元的死亡似乎是受体失活的直接后果。相比之下，CXCR4缺陷动物中运动神经元死亡增加似乎是由于肢体肌发生受损以及随后肌肉源性神经营养支持的丧失所致。总之，我们的研究结果揭示了CXCL12/CXCR4在肢体神经肌肉发育控制中一个此前未被认识到的复杂作用。
