The transcription factor Nfix is essential for normal brain development
The transcription factor Nfix is essential for normal brain development
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DOI：
10.1186/1471-213x-8-52
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发表时间：
2008-05-13
影响因子：
--
通讯作者：
Gronostajski, Richard M.
中科院分区：
文献类型：
--
作者：
Campbell, Christine E.;Piper, Michael;Gronostajski, Richard M.
背景资料：核因子I（NFI）多基因家族编码对许多器官系统的发育至关重要的位点特异性转录因子。我们先前表明，Nfia缺陷小鼠表现出胼胝体发育不全和其他前脑缺陷; Nfia缺陷小鼠在肺成熟方面存在缺陷，并表现出类似于Nfia缺陷动物中所见的胼胝体发育不全和前脑缺陷，而Nfic缺陷小鼠在牙根形成方面存在缺陷。最近的Nfix基因已被破坏，这些研究表明，有很大程度上是未知的缺陷，在大脑和骨骼发育Nfix缺陷mice.Results：在这里，我们表明，破坏Nfix由Cre-recombinase介导的切除的第2外显子的结果在大脑发育的缺陷，不同的Nfia和Nfib KO小鼠。特别是，在Nfix-/-小鼠中未观察到完全的胼胝体发育不全，但在Nfix-/-小鼠的侧脑室中似乎存在过量的异常Pax 6-和doublecortin-阳性细胞，脑重量增加，扣带皮层和整个脑沿着背腹轴的扩张，以及海马的异常形成。在标准实验室食物中，Nfix-/-动物显示从与P8相似到P14的生长速率降低，从与P14相似到P22的体重减轻，并在与P22相似时死亡。如果它们的食物从P10开始补充软面团食物，Nfix-/-动物从P8到P20显示出体重增加的滞后，但随后增加了它们的生长速率。一小部分动物能存活到成年并能生育。体重减轻与延迟眼和耳道开放，并建议在Nfix-/- animals.Conclusion的几个上皮结构的发展延迟：这些数据表明，Nfix是必不可少的正常脑发育，可能需要神经干细胞的稳态。眼睛和耳朵张开的延迟以及脑形态缺陷似乎与营养缺乏无关，因为用软面团挽救围产期致死性并不能消除这些缺陷。
Background: The Nuclear Factor I ( NFI) multi-gene family encodes site-specific transcription factors essential for the development of a number of organ systems. We showed previously that Nfia-deficient mice exhibit agenesis of the corpus callosum and other forebrain defects; Nfib-deficient mice have defects in lung maturation and show callosal agenesis and forebrain defects resembling those seen in Nfia-deficient animals, while Nfic-deficient mice have defects in tooth root formation. Recently the Nfix gene has been disrupted and these studies indicated that there were largely uncharacterized defects in brain and skeletal development in Nfix-deficient mice.Results: Here we show that disruption of Nfix by Cre-recombinase mediated excision of the 2nd exon results in defects in brain development that differ from those seen in Nfia and Nfib KO mice. In particular, complete callosal agenesis is not seen in Nfix-/- mice but rather there appears to be an overabundance of aberrant Pax6-and doublecortin-positive cells in the lateral ventricles of Nfix-/- mice, increased brain weight, expansion of the cingulate cortex and entire brain along the dorsal ventral axis, and aberrant formation of the hippocampus. On standard lab chow Nfix-/- animals show a decreased growth rate from similar to P8 to P14, lose weight from similar to P14 to P22 and die at similar to P22. If their food is supplemented with a soft dough chow from P10, Nfix-/- animals show a lag in weight gain from P8 to P20 but then increase their growth rate. A fraction of the animals survive to adulthood and are fertile. The weight loss correlates with delayed eye and ear canal opening and suggests a delay in the development of several epithelial structures in Nfix-/- animals.Conclusion: These data show that Nfix is essential for normal brain development and may be required for neural stem cell homeostasis. The delays seen in eye and ear opening and the brain morphology defects appear independent of the nutritional deprivation, as rescue of perinatal lethality with soft dough does not eliminate these defects.