The Atoh1-lineage gives rise to hair cells and supporting cells within the mammalian cochlea.
The Atoh1-lineage gives rise to hair cells and supporting cells within the mammalian cochlea.
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DOI：
10.1016/j.ydbio.2013.01.005
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发表时间：
2013-04-01
影响因子：
2.7
通讯作者：
Kelley, Matthew W.
中科院分区：
文献类型：
--
作者：
Driver, Elizabeth Carroll;Sillers, Laura;Coate, Thomas M.;Rose, Matthew F.;Kelley, Matthew W.
位于哺乳动物耳蜗内的Corti器官含有精确的毛细胞(HC)和支持细胞(SC)马赛克，其图案对听觉功能至关重要。在耳蜗管发育的早期阶段，HCs和SCs的前体细胞在耳蜗管的同一有丝分裂后区域被发现，并且在缺乏转录因子Atoh1的小鼠中两者都缺失。根据现有的数据，Atoh1被认为是HC命运的最早决定因素，并在HC分化中具有细胞自主作用，但耳蜗管内Atoh1阳性细胞的谱系尚不清楚。为了解决这个问题，我们使用了一个可诱导的Atoh1Cre*PR等位基因来永久标记不同发育时间点表达Atoh1的细胞。我们发现，来自Atoh1系的高达30%的细胞发展为SCs，并且Atoh1阳性的SCs的数量在空间和时间上都以与持续承诺一致的模式减少。Notch信号的调节是形成HC-SC嵌合体所必需的，它改变了Atoh1谱系中发展为HC或SC的细胞的百分比。HC-SC的比例也受到耳蜗管形态发生的影响，因为抑制耳蜗管的生长会增加发育为SCs的Atoh1系细胞的数量。我们的结果表明，Atoh1谱系是在耳蜗发育的早期建立的，但也表明Atoh1的表达并不绝对导致HC命运的承诺。
The Organ of Corti, located within the mammalian cochlea, contains a precise mosaic of hair cells (HC) and supporting cells (SC), the patterning of which is critical for auditory function. Progenitors of HCs and SCs are found in the same post-mitotic region of the cochlear duct during early stages of cochlear development, and both HCs and SCs are absent in mice lacking the transcription factor Atoh1. Based on existing data, Atoh1 is thought to be the earliest determinant of HC fate, and to have a cell-autonomous role in HC differentiation, but the lineage of Atoh1-positive cells within the cochlear duct remains unclear. To address this issue, we used an inducible Atoh1Cre*PR allele to permanently mark Atoh1-expressing cells at different developmental time points. We found that up to 30% of cells from the Atoh1-lineage develop as SCs, and that the number of Atoh1-positive SCs decreases both spatially and temporally in a pattern consistent with ongoing commitment. Modulation of Notch signaling, necessary for formation of the HC-SC mosaic, changes the percentage of cells from the Atoh1-lineage that develop as either HCs or SCs. The HC-SC ratio is also affected by morphogenesis of the cochlea, as inhibiting the outgrowth of the cochlear duct increases the number of Atoh1-lineage cells that develop as SCs. Our results demonstrate that the Atoh1-lineage is established early in cochlear development, but also show that expression of Atoh1 does not absolutely result in commitment to a HC fate.
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影响因子：
3.7
作者：
Jahan I;Pan N;Kersigo J;Fritzsch B
通讯作者：
Fritzsch B
影响因子：
64.8
作者：
BenArie, N;Bellen, HJ;Zoghbi, HY
通讯作者：
Zoghbi, HY
DOI：
10.1073/pnas.0808175105
发表时间：
2008-11-25
影响因子：
11.1
作者：
Dabdoub, Alain;Puligilla, Chandrakala;Kelley, Matthew W.
通讯作者：
Kelley, Matthew W.
DOI：
10.1523/jneurosci.0312-08.2008
发表时间：
2008-07-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Driver EC;Pryor SP;Hill P;Turner J;Rüther U;Biesecker LG;Griffith AJ;Kelley MW
通讯作者：
Kelley MW
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
通讯作者：
Zeng H