Crosstalk between glucose metabolism and morphogen signalling specifies tonotopic identity in developing hair cells
Crosstalk between glucose metabolism and morphogen signalling specifies tonotopic identity in developing hair cells
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葡萄糖代谢和形态发生素信号传导之间的串扰指定了毛细胞发育中的音调特性
DOI：
10.1101/2022.04.11.487851
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
O'Sullivan J
中科院分区：
文献类型：
--
作者：
O'Sullivan J
在具有细长听觉器官的脊椎动物中，机械感觉毛细胞（hc）的组织使得复杂的声音沿着近端到远端长轴（张力变位）被分解成它们的组成频率。在沿雏鸡耳蜗的适当位置获得频率特异性形态，基底乳头（BP），需要新生hc在发育过程中确定其tonotopic位置。在听觉器官中，发育中的HC与其沿轴的局部生态位之间的复杂信号传导目前知之甚少。在这里，我们应用NAD(P)H荧光寿命成像（FLIM）来揭示沿着发展中的BP的张力轴的代谢梯度。在发育过程中，通过抑制细胞内葡萄糖分解代谢的不同分支点，重塑这些梯度，改变正常的形态因子信号传导，消除张力异位模式，使毛细胞形态沿BP的梯度差异正常化。这些发现强调了形态因子信号传导和代谢重编程之间的因果关系，在发展听觉hc的过程中指定了同种异构体的身份。
In vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along the proximal-to-distal long (tonotopic) axis. Acquisition of frequency-specific morphologies at the appropriate positions along the chick cochlea, the basilar papilla (BP), requires that nascent HCs determine their tonotopic positions during development. The complex signalling within the auditory organ between the developing HC and its local niche along the axis is currently poorly understood. Here we apply NAD(P)H fluorescence lifetime imaging (FLIM) to reveal metabolic gradients along the tonotopic axis of the developing BP. Re-shaping these gradients during development, by inhibiting different branch points of cytosolic glucose catabolism, alters normal morphogen signalling and abolishes tonotopic patterning, normalising the graded differences in hair cell morphology along the BP. These findings highlight a causal link between morphogen signalling and metabolic reprogramming in specifying tonotopic identity in developing auditory HCs.
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DOI：
10.1682/jrrd.2005.01.0006
发表时间：
2005-07-01
影响因子：
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作者：
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DOI：
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发表时间：
1992-01-01
期刊：
ANNUAL REVIEW OF CELL BIOLOGY
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2016-10-06
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2009-04-02
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