Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organisation in the chicken cochlea.
Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organisation in the chicken cochlea.
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DOI：
10.7554/elife.86233
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发表时间：
2023-08-04
期刊：
影响因子：
7.7
通讯作者：
Mann ZF
中科院分区：
文献类型：
--
作者：
O'Sullivan JDB;Blacker TS;Scott C;Chang W;Ahmed M;Yianni V;Mann ZF
在具有细长听觉器官的脊椎动物中，机械感觉毛细胞（HCs）的组织使得复杂的声音沿着近端到远端长（张力异位）轴被分解成它们的组成频率。在沿雏鸡耳蜗的适当位置（基底乳头）获得独特的形态，需要新生hc在发育过程中确定其tonotopic位置。在发育中的HC及其沿耳蜗的局部生态位之间的听觉器官内的复杂信号传导尚不清楚。利用实时成像和NAD(P)H荧光寿命成像显微镜的结合，我们发现糖酵解和戊糖磷酸途径在细胞平衡中沿张力轴发展的hc存在梯度。通过抑制细胞内葡萄糖分解代谢的不同分支来扰乱这种平衡，会破坏发育中的形态因子信号，并消除HC形态中正常的张力梯度。这些发现强调了分级形态因子信号传导和代谢重编程之间的因果关系，以确定发展中的hcc的tonotopic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 a proximal-to-distal long (tonotopic) axis. Acquisition of unique morphologies at the appropriate position along the chick cochlea, the basilar papilla, requires that nascent HCs determine their tonotopic positions during development. The complex signalling within the auditory organ between a developing HC and its local niche along the cochlea is poorly understood. Using a combination of live imaging and NAD(P)H fluorescence lifetime imaging microscopy, we reveal that there is a gradient in the cellular balance between glycolysis and the pentose phosphate pathway in developing HCs along the tonotopic axis. Perturbing this balance by inhibiting different branches of cytosolic glucose catabolism disrupts developmental morphogen signalling and abolishes the normal tonotopic gradient in HC morphology. These findings highlight a causal link between graded morphogen signalling and metabolic reprogramming in specifying the tonotopic identity of developing HCs.