期刊
BLOOD
卷 110, 期 10, 页码 3618-3623出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-06-097030
关键词
-
类别
资金
- NCI NIH HHS [R01 CA097148, R01CA097148, R01CA036167, R01 CA036167] Funding Source: Medline
- NIAID NIH HHS [R01 AI047833, R01AI047833] Funding Source: Medline
Signaling mediated by various Notch receptors and their ligands regulates diverse biological processes, including lymphoid cell fate decisions. Notch1 is required during T-cell development, while Notch2 and the Notch ligand Delta-likel1 control marginal zone B (MZB) cell development. We previously determined that Mastermind-like (MAML) transcriptional coactivators are required for Notch-induced transcription by forming ternary nuclear complexes with Notch and the transcription factor CSL. The 3 MAML family members (MAML1-MAML3) are collectively essential for Notch activity in vivo, but whether individual MAMLs contribute to the specificity of Notch functions is unknown. Here, we addressed this question by studying lymphopoiesis in the absence of the Maml1 gene. Since Maml1(-/-) mice suffered perinatal lethality, hematopoietic chimeras were generated with Maml1(-/-), Maml1(+/-), or wild-type fetal liver progenitors. Maml1 deficiency minimally affected T-cell development, but was required for the development of MZB cells, similar to the phenotype of Notch2 deficiency. Moreover, the number of MZB cells correlated with Maml1 gene dosage. Since all 3 Maml genes were expressed in MZB cells and their precursors, these results suggest that Maml1 is specifically required for Notch2 signaling in MZB cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据