GAP-43 heterozygous mice show delayed barrel patterning, differentiation of radial glia, and downregulation of GAP-43.
GAP-43 heterozygous mice show delayed barrel patterning, differentiation of radial glia, and downregulation of GAP-43.
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GAP-43 杂合小鼠表现出桶状模式延迟、放射状胶质细胞分化和 GAP-43 下调。
DOI：
10.1002/ar.a.20291
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
McCasland,JamesS
中科院分区：
文献类型：
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作者：
McIlvain,Vera;McCasland,JamesS
GAP-43杂合子(HZ)小鼠在出生后第7天表现出异常的丘脑皮质寻路、震颤和终末树枝形成(P7)。在这里，我们测试了这些缺陷是否与HZ皮质模式发育延迟有关。我们评估了野生型(WT)和HZ皮质中桶状分离和放射状胶质细胞分化的比率。由于GAP-43参与了某些形式的神经可塑性，我们还比较了两种类型的病变诱导可塑性的关键期的持续时间。细胞色素氧化酶组织化学显示，在GAP-43 HZ小鼠中桶形图案的形成延迟了大约1天。GAP-43 WT桶在P2-P3之间出现完全偏析，而HZ桶直到P3-P4才达到相同的偏析水平。我们发现放射状胶质细胞从单极表型到多极表型的转变也有类似的延迟，从WT的P5到HZ皮质的P7。放射状神经胶质细胞代表着许多发育中的皮质神经前体细胞，并帮助细胞迁移。因此，放射状胶质细胞分化的延迟可能是HZ桶状分离延迟的原因之一。有趣的是，我们没有发现HZ大脑皮层对早期周围损伤反应的临界期的范围或大脑皮层反应的时间进程的变化。正如预期的那样，在发育早期，HZ皮质中GAP-43的表达显著减少。然而，HZ GAP-43的表达在P9之后保持在最高水平，而此时它通常是下调的。结果，HZ GAP-43的表达在P26时接近正常，此时桶的尺寸已恢复到接近正常的水平。我们的研究结果表明，GAP-43缺乏会导致发育的早期延迟，并提示这些失败之后会出现动态平衡反应，包括延长GAP-43的表达。这些代偿机制可能挽救新生儿正常的皮质重组和成年后接近正常的桶状结构和GAP-43的表达。©2006 Wiley-Liss，Inc.
GAP‐43 heterozygous (HZ) mice exhibit abnormal thalamocortical pathfinding, fasciculation, and terminal arborization at postnatal day 7 (P7). Here we tested whether these defects are correlated with delayed development of HZ cortical patterns. We assessed the rate of barrel segregation and radial glia differentiation in wild‐type (WT) and HZ cortices. Since GAP‐43 is involved in some forms of neural plasticity, we also compared the duration of the critical period for lesion‐induced plasticity in both genotypes. Cytochrome oxidase histochemistry revealed a delay of approximately 1 day in barrel pattern formation in GAP‐43 HZ mice. GAP‐43 WT barrels showed complete segregation between P2–P3, while HZ barrels did not reach the same level of segregation until P3–P4. We found a similar delay in the transformation of radial glia from monopolar to multipolar phenotypes, from P5 in WT to P7 in HZ cortex. Radial glial cells represent many of the neuronal progenitors in developing cortex and aid in cell migration. Thus, the delay in radial glial differentiation may contribute to the delay in HZ barrel segregation. Interestingly, we found no change in the extent of the critical period for HZ cortical responsiveness to early peripheral damage or in the time course of the cortical response. As expected, GAP‐43 expression in HZ cortex is significantly reduced early in development. However, HZ GAP‐43 expression remains at maximum levels after P9, when it is normally downregulated. As a result, HZ GAP‐43 expression is near‐normal by P26, by which time near‐normal barrel dimensions have been restored. Our findings indicate that GAP‐43 deficiency leads to early delays in barrel development and suggest that these failures are followed by homeostatic responses, including prolonged GAP‐43 expression. These compensatory mechanisms may rescue normal cortical reorganization in neonates and near‐normal barrel morphology and GAP‐43 expression in adulthood. © 2006 Wiley‐Liss, Inc.