Earmuff maintains restricted potentials of mature secondary neuroblasts

耳罩维持成熟次级神经母细胞的受限潜力

基本信息

批准号：
8655546
负责人：
Cheng-Yu Lee
金额：
$ 29.45万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-01 至 2015-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The mechanisms that restrict proliferation and suppress de-differentiation of transit amplifying cells in adult stem cell lineages are unknown. Mature secondary neuroblasts in Drosophila larval brains resemble vertebrate transit amplifying cells, and undergo limited rounds of asymmetric divisions to regenerate and to produce terminally differentiated neurons. We identified a novel transcription factor Earmuff (Erm), which restricts proliferation and suppresses de-differentiation of mature secondary neuroblasts. In erm mutant brains, mature secondary neuroblasts de-differentiate back into their parental neuroblast fates resulting in a dramatic increase in type II neuroblasts. The physiological and functional properties of the de-differentiated neuroblasts are indistinguishable from the endogenous type II neuroblasts. The de-differentiation phenotype in erm mutant brains can be rescued by targeted expression of Erm or its mouse homologs in mature secondary neuroblasts. Intriguingly, de-differentiation of mature secondary neuroblasts in erm mutant brains occurs independently of cortical cell polarity. Our data suggest that Erm restricts proliferation by promoting Prospero-mediate cell cycle exit, but suppresses de-differentiation by negatively regulating Notch signaling. Our proposal outlined below will provide insight into the molecular mechanisms by which Erm restricts proliferation and suppresses de-differentiation of mature secondary neuroblasts.

描述（由申请人提供）：限制和抑制成年干细胞谱系中传输扩增细胞的扩散和抑制的机制尚不清楚。果蝇幼虫大脑中的成熟二级神经细胞类似于脊椎动物的放大细胞，并且经历了有限的不对称分裂回合以再生并产生终极分化的神经元。我们确定了一种新型的转录因子耳罩（ERM），该因子限制了增殖并抑制成熟次生神经细胞的差异化。在ERM突变大脑中，成熟的二级神经细胞将分化的归化回到其亲本神经细胞命运中，从而导致II型神经细胞的急剧增加。去分化神经细胞的生理和功能特性与内源性II型神经细胞没有区别。 ERM突变体大脑中的脱节表型可以通过成熟的次生神经细胞中的ERM或其小鼠同源物的靶向表达来挽救。有趣的是，ERM突变大脑中成熟的次生神经细胞的脱不同是独立于皮质细胞极性发生的。我们的数据表明，ERM通过促进Prospero-Mediate细胞周期退出来限制增殖，但通过负调节Notch信号传导来抑制脱节。我们下面概述的我们的建议将洞悉ERM限制增殖并抑制成熟二级神经细胞的脱不同的分子机制。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

An Hdac1/Rpd3-Poised Circuit Balances Continual Self-Renewal and Rapid Restriction of Developmental Potential during Asymmetric Stem Cell Division.

DOI：
10.1016/j.devcel.2017.01.014
发表时间：
2017-02-27
期刊：
Developmental cell
影响因子：
11.8
作者：
Janssens DH;Hamm DC;Anhezini L;Xiao Q;Siller KH;Siegrist SE;Harrison MM;Lee CY
通讯作者：
Lee CY

dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila.