Numb is not a critical regulator of Notch-mediated cell fate decisions in the developing chick inner ear.
Numb is not a critical regulator of Notch-mediated cell fate decisions in the developing chick inner ear.
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DOI：
10.3389/fncel.2015.00074
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发表时间：
2015
影响因子：
5.3
通讯作者：
Daudet N
中科院分区：
文献类型：
--
作者：
Eddison M;Weber SJ;Ariza-McNaughton L;Lewis J;Daudet N
Notch信号通路控制脊椎动物内耳中毛细胞和支持细胞的分化。在这里，我们已经调查了是否Numb，一个已知的调节器的Notch活动在果蝇，参与这一过程中的鸡胚。鸡的同源Numb在整个耳囊的早期发展阶段的表达，并集中在基底极的细胞。它在某些细胞分裂中是不对称分配的，如在果蝇中，这表明它可以作为两个子细胞之一继承的决定因素，并有利于采用毛细胞的命运。为了测试Numb在毛细胞命运决定和Notch信号转导调节中的意义，我们使用不同的方法在内耳发育的不同阶段过表达Numb。我们发现，持续或晚期Numb过表达不会促进毛细胞分化，并且Numb不会阻止Notch信号的接收。令人惊讶的是，没有一个过度表达Numb的细胞分化成毛细胞，这表明高水平的Numb蛋白可能会干扰毛细胞存活所必需的细胞内过程。然而，当Numb在耳朵发育早期和更短暂地过表达时，没有观察到对毛细胞形成的影响。这些结果表明，至少在内耳中，Numb不会显著抑制Notch活性，并且其在分裂的前体细胞中的不对称分布不会控制毛细胞和支持细胞命运之间的选择。
The Notch signaling pathway controls differentiation of hair cells and supporting cells in the vertebrate inner ear. Here, we have investigated whether Numb, a known regulator of Notch activity in Drosophila, is involved in this process in the embryonic chick. The chicken homolog of Numb is expressed throughout the otocyst at early stages of development and is concentrated at the basal pole of the cells. It is asymmetrically allocated at some cell divisions, as in Drosophila, suggesting that it could act as a determinant inherited by one of the two daughter cells and favoring adoption of a hair-cell fate. To test the implication of Numb in hair cell fate decisions and the regulation of Notch signaling, we used different methods to overexpress Numb at different stages of inner ear development. We found that sustained or late Numb overexpression does not promote hair cell differentiation, and Numb does not prevent the reception of Notch signaling. Surprisingly, none of the Numb-overexpressing cells differentiated into hair cells, suggesting that high levels of Numb protein could interfere with intracellular processes essential for hair cell survival. However, when Numb was overexpressed early and more transiently during ear development, no effect on hair cell formation was seen. These results suggest that in the inner ear at least, Numb does not significantly repress Notch activity and that its asymmetric distribution in dividing precursor cells does not govern the choice between hair cell and supporting cell fates.
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影响因子：
64.5
作者：
CHENN, A;MCCONNELL, SK
通讯作者：
MCCONNELL, SK
影响因子：
16.2
作者：
Das, T;Payer, B;Harris, WA
通讯作者：
Harris, WA
影响因子：
3.7
作者：
Freeman SD;Daudet N
通讯作者：
Daudet N
DOI：
10.1002/neu.10176
发表时间：
2003-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Dooley, CM;James, J;Ahmad, I
通讯作者：
Ahmad, I
影响因子：
11.8
作者：
Berdnik, D;Török, T;Knoblich, JA
通讯作者：
Knoblich, JA