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The transcription factors JUN (the target of the c-Jun N-terminal kinases, JNKs) and DDIT3\/CHOP (a mediator of the endoplasmic reticulum stress response) have been shown to control the majority of proapoptotic signaling after mechanical axonal injury in RGCs and in other models of neurodegeneration. The downstream transcriptional networks controlled by JUN and DDIT3, which are critical for RGC death, however, are not well defined. To determine these networks, RNA was isolated from the retinas of wild-type mice and mice deficient in <jats:italic>Jun<\/jats:italic>, <jats:italic>Ddit3<\/jats:italic>, and both <jats:italic>Jun<\/jats:italic> and <jats:italic>Ddit3<\/jats:italic> three days after mechanical optic nerve crush injury (CONC). RNA-sequencing data analysis was performed and immunohistochemistry was used to validate potential transcriptional signaling changes after axonal injury. This study identified downstream transcriptional changes after injury including both neuronal survival and proinflammatory signaling that were attenuated to differing degrees by loss of <jats:italic>Ddit3<\/jats:italic>, <jats:italic>Jun<\/jats:italic>, and <jats:italic>Ddit3\/Jun<\/jats:italic>. These data suggest proinflammatory signaling in the retina might be secondary to activation of pro-death pathways in RGCs after acute axonal injury. These results determine the downstream transcriptional networks important for apoptotic signaling which may be important for ordering and staging the pro-degenerative signals after mechanical axonal injury.<\/jats:p>","DOI":"10.1038\/s41419-022-04666-3","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T14:04:38Z","timestamp":1647439478000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Transcriptional control of retinal ganglion cell death after axonal injury"],"prefix":"10.1038","volume":"13","author":[{"given":"Stephanie B.","family":"Syc-Mazurek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongtian Stanley","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0078-6088","authenticated-orcid":false,"given":"Olivia J.","family":"Marola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-6474","authenticated-orcid":false,"given":"Gareth R.","family":"Howell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2844-7632","authenticated-orcid":false,"given":"Richard T.","family":"Libby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"4666_CR1","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1083\/jcb.200706181","volume":"179","author":"GR Howell","year":"2007","unstructured":"Howell GR, Libby RT, Jakobs TC, Smith RS, Phalan FC, Barter JW, et al. 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