Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland 21218, USA.
Nat Commun. 2017 Apr 20;8:15098. doi: 10.1038/ncomms15098.
B-type lamins are major constituents of the nuclear lamina in all metazoan cells, yet have specific roles in the development of certain cell types. Although they are speculated to regulate gene expression in developmental contexts, a direct link between B-type lamins and developmental gene expression in an in vivo system is currently lacking. Here, we identify lamin B1 as a key regulator of gene expression required for the formation of functional olfactory sensory neurons. By using targeted knockout in olfactory epithelial stem cells in adult mice, we show that lamin B1 deficient neurons exhibit attenuated response to odour stimulation. This deficit can be explained by decreased expression of genes involved in mature neuron function, along with increased expression of genes atypical of the olfactory lineage. These results support that the broadly expressed lamin B1 regulates expression of a subset of genes involved in the differentiation of a specific cell type.
B 型核纤层蛋白是所有后生动物细胞核纤层的主要成分，但在某些细胞类型的发育中具有特定作用。尽管人们推测它们在发育环境中调节基因表达，但目前在体内系统中，B 型核纤层蛋白与发育基因表达之间缺乏直接联系。在这里，我们确定 lamin B1 是形成功能性嗅觉感觉神经元所必需的基因表达的关键调节剂。通过在成年小鼠的嗅上皮干细胞中使用靶向敲除，我们发现 lamin B1 缺失的神经元对气味刺激的反应减弱。这种缺陷可以通过参与成熟神经元功能的基因表达减少以及不典型的嗅觉谱系基因表达增加来解释。这些结果支持广泛表达的 lamin B1 调节参与特定细胞类型分化的一组基因的表达。
