{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T12:32:11Z","timestamp":1768739531341,"version":"3.49.0"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T00:00:00Z","timestamp":1399334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001677","name":"National Institute of Health and Medical Research","doi-asserted-by":"publisher","award":["EY017061 and EY018868"],"award-info":[{"award-number":["EY017061 and EY018868"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p><jats:styled-content>Background: <\/jats:styled-content>Heparan sulfate proteoglycans (HSPG) are important for embryonic development by means of the regulation of gradient formation and signaling of multiple growth factors and morphogens. Previous studies have shown that Bmp\/Shh\/Fgf signaling are required for the regionalization of the optic vesicle (OV) and for the closure of the optic fissure (OF), the disturbance of which underlie ocular anomalies such as microphthalmia, coloboma, and optic nerve hypoplasia. <jats:styled-content>Results:<\/jats:styled-content>To study HSPG\u2010dependent coordination of these signaling pathways during mammalian visual system development, we have generated a series of OV\u2010specific mutations in the heparan sulfate (HS) <jats:italic>N<\/jats:italic>\u2010sulfotransferase genes (<jats:italic>Ndst1<\/jats:italic> and <jats:italic>Ndst2<\/jats:italic>) and HS <jats:italic>O<\/jats:italic>\u2010sulfotransferase genes (<jats:italic>Hs2st<\/jats:italic>, <jats:italic>Hs6st1<\/jats:italic>, and <jats:italic>Hs6st2<\/jats:italic>) in mice. Of interest, the resulting HS undersulfation still allowed for normal retinal neurogenesis and optic fissure closure, but led to defective optic disc and stalk development. The adult mutant animals further developed optic nerve aplasia\/hypoplasia and displayed retinal degeneration. We observed that MAPK\/ERK signaling was down\u2010regulated in <jats:italic>Ndst<\/jats:italic> mutants, and consistent with this, HS\u2010related optic nerve morphogenesis defects in mutant mice could partially be rescued by constitutive Kras activation. <jats:styled-content>Conclusions:<\/jats:styled-content> These results suggest that HSPGs, depending on their HS sulfation pattern, regulate multiple signaling pathways in optic disc and stalk morphogenesis. <jats:italic>Developmental Dynamics 243:1310\u20131316, 2014<\/jats:italic>. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.24142","type":"journal-article","created":{"date-parts":[[2014,4,19]],"date-time":"2014-04-19T07:13:08Z","timestamp":1397891588000},"page":"1310-1316","source":"Crossref","is-referenced-by-count":21,"title":["Role of heparan sulfate proteoglycans in optic disc and stalk morphogenesis"],"prefix":"10.1002","volume":"243","author":[{"given":"Zhigang","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Glick Eye Institute, Indiana University School of Medicine Indianapolis Indiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kay","family":"Grobe","sequence":"additional","affiliation":[{"name":"Physiological Chemistry and Pathobiochemistry University of Muenster M\u00fcnster Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Pathology, and Cell Biology Columbia University New York New 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