{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:22:14Z","timestamp":1791303734355,"version":"4.1.0"},"reference-count":20,"publisher":"National Academy of Sciences","issue":"36","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,9,4]]},"abstract":"<jats:p>Conditioning lesion of the peripheral branch of dorsal column axons is a well-known paradigm enabling the central branch to regenerate after injury to the spinal cord. However, only a small number of regenerating axons enter grafted substrates, and they do not grow beyond the lesion. We found that conditioning lesion induces, in addition to growth-stimulating genes, related to receptor tyrosine kinase (Ryk), a potent repulsive receptor for Wnts. Wnts are expressed around the site of spinal cord injury, and we found that grafted bone marrow stromal cells secreting the Wnt inhibitors secreted frizzled-related protein 2 or Wnt inhibitory factor 1 enhanced regeneration of the central branch after peripheral conditioning lesion. Furthermore, we found that Wnt4-expressing grafts caused dramatic long-range retraction of the injured central branch of conditioned dorsal root ganglion neurons. Macrophages accumulate along the path of receding axons but not around Wnt4-expressing cells, suggesting that the retraction of dorsal column axons is not a secondary effect of increased macrophages attracted by Wnt4. Therefore, Wnt-Ryk signaling is an inhibitory force co-induced with growth-stimulating factors after conditioning lesion. Overcoming Wnt inhibition may further enhance therapies being designed on the basis of the conditioning-lesion paradigm.<\/jats:p>","DOI":"10.1073\/pnas.1206218109","type":"journal-article","created":{"date-parts":[[2012,8,18]],"date-time":"2012-08-18T01:22:24Z","timestamp":1345252944000},"page":"14663-14668","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":57,"title":["Reinduced Wnt signaling limits regenerative potential of sensory axons in the spinal cord following conditioning lesion"],"prefix":"10.1073","volume":"109","author":[{"suffix":"II","given":"Edmund R.","family":"Hollis","sequence":"first","affiliation":[{"name":"Neurobiology Section, Biological Sciences Division, University of California at San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Zou","sequence":"additional","affiliation":[{"name":"Neurobiology Section, Biological Sciences Division, University of California at San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,8,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/309791a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05597.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1939-08.2008"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00623"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3257-09.2009"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05859.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2981-04.2004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4906-07.2008"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0738"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2006.1892"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90160-6"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.07.019"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4508-10.2010"},{"key":"e_1_3_3_14_2","doi-asserted-by":"crossref","unstructured":"ER Hollis Y Zou Expression of the Wnt signaling system in central nervous system axon guidance and regeneration. 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