{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:14:41Z","timestamp":1787807681333,"version":"build-2784847793"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"22","license":[{"start":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T00:00:00Z","timestamp":1684713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"HHS | NIH | National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01 DC015799"],"award-info":[{"award-number":["R01 DC015799"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,5,30]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.2217595120","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T15:02:10Z","timestamp":1684767730000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["EGR4 is critical for cell-fate determination and phenotypic maintenance of geniculate ganglion neurons underlying sweet and umami taste"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5521-9865","authenticated-orcid":false,"given":"Debarghya","family":"Dutta Banik","sequence":"first","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis J.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Soboloff","sequence":"additional","affiliation":[{"name":"Department of Cancer &amp; Cellular Biology, Fels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren G.","family":"Tourtellotte","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Neurology, and Neurological Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Pierchala","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell Biology &amp; Physiology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2023,5,22]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2010.09.003"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0901-11.2011"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.03.006"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00304"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2006.12.007"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110416108"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708838115"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01095-1"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.031"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053399"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2008-0611"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/chemse\/bjx032"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","unstructured":"J. M. D. Olmsted Effects of cutting the lingual nerve of the dog. J. Comp. Neurol. 33 149\u2013154 (1921) 10.1002\/cne.900330204.","DOI":"10.1002\/cne.900330204"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","unstructured":"J. H. M. Vintschgau J. Honigschmied Nervus Glossopharyngeus und Schmeckbecher. Archiv f\u00fcr die gesamte Physiologie des Menschen und der Tiere. 14 443\u2013448 (1877) 10.1007\/BF01635485.","DOI":"10.1007\/BF01635485"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902600206"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.07-07-02075.1987"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901720405"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091300104"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1719109115"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","unstructured":"X. Lin R-spondin substitutes for neuronal input for taste cell regeneration in adult mice. Proc. Natl. Acad. Sci. U.S.A. 118 e2001833118 (2021). e2001833118","DOI":"10.1073\/pnas.2001833118"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006442"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907143106"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102700"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990621)409:1<13::AID-CNE2>3.0.CO;2-O"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-8-S3-S4"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.22.5061"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.13.2421"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","unstructured":"D. Dutta Banik K. F. Medler Taste receptor signaling. Handb. Exp. Pharmacol. 275 33\u201352 (2021) 10.1007\/164_2021_442.","DOI":"10.1007\/164_2021_442"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5320(69)80043-2"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1070260304"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20954"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718802115"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4973-06.2007"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1174601"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/75556"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1113"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2016.343"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07746-z"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00866"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.20.4065"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2008.05.008"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0717-07.2007"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083460"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2015.07.006"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0097-15.2015"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2017.06.001"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2006-10.2011"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/641248"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.09.004"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1712881114"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061341"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0612-07.2007"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-14-05982.2002"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23299"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008925"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2021.01.010"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_4_58_2","unstructured":"D. D. Banik B. A. Pierchala EGR4 is critical for cell-fate determination and maintenance of Geniculate Ganglion neurons underlying sweet and umami taste. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE223724. Deposited 25 January 2023."},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks042"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2217595120","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:17:26Z","timestamp":1695287846000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2217595120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,22]]},"references-count":61,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2023,5,30]]}},"alternative-id":["10.1073\/pnas.2217595120"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2217595120","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,22]]},"assertion":[{"value":"2022-10-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2217595120"}}