EGR4 is critical for cell-fate determination and phenotypic maintenance of geniculate ganglion neurons underlying sweet and umami taste.
EGR4 is critical for cell-fate determination and phenotypic maintenance of geniculate ganglion neurons underlying sweet and umami taste.
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DOI：
10.1073/pnas.2217595120
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发表时间：
2023-05-30
影响因子：
11.1
通讯作者：
Pierchala, Brian A.
中科院分区：
文献类型：
--
作者：
Banik, Debarghya Dutta;Martin, Louis J.;Tang, Tao;Soboloff, Jonathan;Tourtellotte, Warren G.;Pierchala, Brian A.
我们对口腔感觉神经元的发展和多样化的理解是基本的。膝状体神经节（GG）的口部投射神经元从味蕾到脑干投射五种味觉。对这些刺激作出反应的独特神经元亚群的多样化的转录调控机制仍然难以捉摸。在这里，我们证明了EGR 4，锌指转录因子，在细胞命运的规范和维护选择性亚群的GG口腔感觉神经元起着至关重要的作用。EGR 4还需要维持味蕾的适当神经支配，以及相应的味蕾细胞亚型，这些味蕾细胞亚型是甜味和鲜味的基础。味觉开始于化学刺激激活味蕾中的受体细胞，然后通过神经支配口腔感觉神经元将该信号传递到CNS。口腔感觉神经元的胞体位于膝状神经节（GG）和结状/岩/颈静脉神经节。膝状神经节包含两个主要的神经元群体：支配耳廓的BRN 3A+体感神经元和支配口腔的PHOX 2B+感觉神经元。虽然对不同的味蕾细胞亚型了解很多，但对PHOX 2B+感觉亚群的分子身份知之甚少。在GG，多达12个不同的亚群已被预测从电生理学研究，而转录身份存在的只有3至6。重要的是，使PHOX 2B+口腔感觉神经元多样化为这些亚群的细胞命运途径是未知的。转录因子EGR 4被鉴定为在GG神经元中高度表达。EGR 4缺失导致GG口腔感觉神经元失去PHOX 2B和其他口腔感觉基因的表达，并上调BRN 3A。随后是味蕾的化学感觉神经支配的损失，响应于苦、甜和鲜味刺激的II型味觉细胞的损失，以及I型神经胶质样味蕾细胞的伴随增加。这些缺陷最终导致对甜味和鲜味的神经反应丧失。总之，我们确定了EGR 4在细胞命运规范和GG神经元亚群的维持中的关键作用，这反过来又维持了适当的甜味和鲜味受体细胞。
Our understanding of the development and diversification of oral sensory neurons that underly the sense of taste is rudimentary. The oral projecting neurons of the geniculate ganglia (GG) transduce the five taste qualities from their origin in taste buds to the brainstem. The transcriptional regulatory mechanisms underlying diversification of the unique neuronal subpopulations responsive to these stimuli remain elusive. Here, we demonstrate the EGR4, a zinc-finger transcription factor, plays a critical role in cell-fate specification and maintenance of selective subpopulations of GG oral sensory neurons. EGR4 is also required to maintain their proper innervation of taste buds, as well as the corresponding taste bud cell subtypes that underlie sweet and umami taste qualities. The sense of taste starts with activation of receptor cells in taste buds by chemical stimuli which then communicate this signal via innervating oral sensory neurons to the CNS. The cell bodies of oral sensory neurons reside in the geniculate ganglion (GG) and nodose/petrosal/jugular ganglion. The geniculate ganglion contains two main neuronal populations: BRN3A+ somatosensory neurons that innervate the pinna and PHOX2B+ sensory neurons that innervate the oral cavity. While much is known about the different taste bud cell subtypes, considerably less is known about the molecular identities of PHOX2B+ sensory subpopulations. In the GG, as many as 12 different subpopulations have been predicted from electrophysiological studies, while transcriptional identities exist for only 3 to 6. Importantly, the cell fate pathways that diversify PHOX2B+ oral sensory neurons into these subpopulations are unknown. The transcription factor EGR4 was identified as being highly expressed in GG neurons. EGR4 deletion causes GG oral sensory neurons to lose their expression of PHOX2B and other oral sensory genes and up-regulate BRN3A. This is followed by a loss of chemosensory innervation of taste buds, a loss of type II taste cells responsive to bitter, sweet, and umami stimuli, and a concomitant increase in type I glial-like taste bud cells. These deficits culminate in a loss of nerve responses to sweet and umami taste qualities. Taken together, we identify a critical role of EGR4 in cell fate specification and maintenance of subpopulations of GG neurons, which in turn maintain the appropriate sweet and umami taste receptor cells.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
味道神经元由大的TRKB受体依赖性和小型TRKB受体独立的亚群组成。
影响因子：
3.7
作者：
Fei D;Krimm RF
通讯作者：
Krimm RF
影响因子：
9
作者：
通讯作者：
--
影响因子：
16.6
作者：
Dvoryanchikov G;Hernandez D;Roebber JK;Hill DL;Roper SD;Chaudhari N
通讯作者：
Chaudhari N
影响因子：
3.1
作者：
Ludwig A;Uvarov P;Pellegrino C;Thomas-Crusells J;Schuchmann S;Saarma M;Airaksinen MS;Rivera C
通讯作者：
Rivera C