Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, 80131 Naples, Italy.
Exp Cell Res. 2011 Feb 15;317(4):464-73. doi: 10.1016/j.yexcr.2010.11.006. Epub 2010 Nov 18.
Krüppel-like factor 7 (KLF7) belongs to the large family of KLF transcription factors, which comprises at least 17 members. Within this family, KLF7 is unique since its expression is strictly restricted within the nervous system during development. We have previously shown that KLF7 is required for neuronal morphogenesis and axon guidance in selected regions of the nervous system, including hippocampus, olfactory bulbs and cortex, as well as in neuronal cell cultures. In the present work, we have furthered our analysis of the role of KLF7 in central nervous system development. By gene expression analysis during brain embryogenesis, we found significant alterations in dopaminergic neurons in Klf7 null mice. In particular, the tyrosine hydroxylase (TH) and dopamine transporter (Dat) transcripts are strongly decreased in the olfactory bulbs and ventral midbrain at birth, compared to wild-type littermates. Interestingly, Klf7-mutant mice show a dramatic reduction of TH-positive neurons in the olfactory bulbs, but no change in GABAergic or midbrain dopaminergic neurons. These observations raise the possibility that a lack of a KLF family member affects dopaminergic neuron development.
Krüppel 样因子 7（KLF7）属于 KLF 转录因子大家族，该家族至少包含 17 个成员。在这个家族中，KLF7 是独一无二的，因为它的表达在发育过程中严格局限于神经系统内。我们之前的研究表明，KLF7 对于选定的神经系统区域（包括海马体、嗅球和大脑皮层）以及神经元细胞培养物中的神经元形态发生和轴突导向是必需的。在本工作中，我们进一步分析了 KLF7 在中枢神经系统发育中的作用。通过胚胎期大脑的基因表达分析，我们发现 Klf7 缺失小鼠的多巴胺能神经元发生了显著改变。特别是，与野生型同窝仔鼠相比，出生时嗅球和腹侧中脑的酪氨酸羟化酶（TH）和多巴胺转运体（Dat）转录本强烈减少。有趣的是，Klf7 突变小鼠的嗅球中 TH 阳性神经元明显减少，但 GABA 能神经元或中脑多巴胺能神经元没有变化。这些观察结果提出了一种可能性，即缺乏 KLF 家族成员可能会影响多巴胺能神经元的发育。
