Increased apoptosis of motoneurons and altered somatotopic maps in the brachial spinal cord of Hoxc-8-deficient mice.
Increased apoptosis of motoneurons and altered somatotopic maps in the brachial spinal cord of Hoxc-8-deficient mice.
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发表时间：
1998-01
期刊：
影响因子：
4.6
通讯作者：
L. Tiret;H. Le Mouellic;M. Maury;P. Brûlet
中科院分区：
文献类型：
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作者：
L. Tiret;H. Le Mouellic;M. Maury;P. Brûlet
同源异型基因Hoxc-8缺陷的小鼠患有先天性前爪伸展缺陷。在胚胎发育过程中，Hoxc-8在脊髓C7至T1节段内的运动神经元中高度表达。这些运动神经元支配前肢远端肌肉，使前爪运动。在Hoxc-8突变胚胎中，这些肌肉的形成是正常的，但它们的神经支配受到干扰。从E13.5开始，通常由C（7-8）MN供应的远端肌肉也接受来自C（5-6）和T1运动神经元的异位投射。运动池的坐标沿吻尾轴和内外侧轴沿着改变。在这种异常的连接模式和自然发生的细胞死亡期间，C7-T1运动神经元中的凋亡特异性增强。Hox编码的区域规格的损失随后导致运动神经元的数量赤字和不可逆转的解体的运动池。在Hoxc-8无效突变体中，C（7-8）运动神经元在生长锥寻路行为和/或靶识别中失去其选择性优势，这是建立和维持功能性神经系统的两个基本步骤。
Mice deficient for the homeotic gene Hoxc-8 suffer from a congenital prehension deficiency of the forepaw. During embryogenesis, Hoxc-8 is highly expressed in motoneurons within spinal cord segments C7 to T1. These motoneurons innervate forelimb distal muscles that move the forepaw. In Hoxc-8 mutant embryos, formation of these muscles is normal, but their innervation is perturbed. From E13.5 onwards, distal muscles normally supplied by C(7-8) MNs also receive ectopic projections from C(5-6) and T1 motoneurons. Coordinates of motor pools are altered along the rostrocaudal and also the mediolateral axes. Following this aberrant connectivity pattern and during the time of naturally occurring cell death, apoptosis is specifically enhanced in C7-T1 motoneurons. Loss of Hox-encoded regional specifications subsequently leads to a numerical deficit of motoneurons and an irreversible disorganization of motor pools. In Hoxc-8 null mutants, C(7-8) motoneurons lose their selective advantage in growth cone pathfinding behavior and/or target recognition, two essential steps in the establishment and maintenance of a functional nervous system.