Diverse developing mouse lineages exhibit high-level c-Myb expression in immature cells and loss of expression upon differentiation
Diverse developing mouse lineages exhibit high-level c-Myb expression in immature cells and loss of expression upon differentiation
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DOI：
10.1038/sj.onc.1202387
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发表时间：
1999-01-28
期刊：
影响因子：
8
通讯作者：
Aronow, BJ
中科院分区：
文献类型：
--
作者：
Ess, KC;Witte, DP;Aronow, BJ
C-myb基因编码胎儿造血所需的序列特异性反式激活因子，但它在其他组织中的潜在作用尚不清楚，因为c-myb基因靶向缺失的小鼠早期胚胎死亡，以及对c-myb表达模式的了解不完全。在造血系统中，c-Myb蛋白作用于靶基因，而靶基因的表达仅限于单个谱系，尽管Myb在多个不成熟谱系中存在和发挥作用。这表明c-Myb在不同细胞类型的特定环境中的作用受到组合相互作用的强烈影响，为了考虑类似的c-Myb作用可能延伸到其他细胞和组织中的非造血系统的可能性，我们用原位杂交的方法研究了c-myb在发育中和成年小鼠中的表达，并将其与阶段特异性分化和有丝分裂活动相关联。不同的组织在发育过程中表现出c-myb的强表达，特别是牙蕾、甲状腺原基、发育中的气管和近端分支呼吸道上皮、毛囊、造血细胞和胃肠隐窝上皮细胞，后三种细胞都在成年期保持高表达。但在未成熟细胞系的终末分化之前有其特有的限制。在所有部位，在胎儿期和成人期，c-Myb表达的缺失与终末分化的启动显著相关，但与有丝分裂活性的丧失无关。基于这些数据，我们假设c-Myb在细胞分化过程中的功能既是未成熟基因表达的激活因子，也是不同谱系中末端分化的抑制因子。
The c-myb gene encodes a sequence specific transactivator that is required for fetal hematopoiesis, but its potential role in other tissues is less clear because of the early fetal demise of mice with targeted deletions of the c-myb gene and incomplete of knowledge about c-myb's expression pattern. In the hematopoietic system, c-Myb protein acts on target genes whose expression is restricted to individual lineages, despite Myb's presence and role in multiple immature lineages. This suggests that c-Myb actions within different cell type-specific contexts are strongly affected by combinatorial interactions, To consider the possibility of similar c-Myb actions could extend into non-hematopoietic systems in other cell and tissue compartments, we characterized c-myb expression in developing and adult mice using in situ hybridization and correlated this with stage-specific differentiation and mitotic activity, Diverse tissues exhibited strong c-myb expression during development, notably tooth buds, the thyroid primordium, developing trachea and proximal branching airway epithelium, hair follicles, hematopoietic cells, and gastrointestinal crypt epithelial cells, The latter three of these all maintained high expression into adulthood, but with characteristic restriction to immature cell lineages prior to their terminal differentiation. In all sites, during fetal and adult stages, loss of c-Myb expression correlated strikingly with the initiation of terminal differentiation, but not the loss of mitotic activity. Based on these data, we hypothesize that c-Myb's function during cellular differentiation is both an activator of immature gene expression and a suppressor of terminal differentiation in diverse lineages.