{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:45:30Z","timestamp":1791164730011,"version":"4.1.0"},"reference-count":72,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,8,28]],"date-time":"2002-08-28T00:00:00Z","timestamp":1030492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"DFG","award":["Ta115\/8-2"],"award-info":[{"award-number":["Ta115\/8-2"]}]},{"name":"DFG","award":["Ta115\/11-1"],"award-info":[{"award-number":["Ta115\/11-1"]}]},{"name":"DFG","award":["SFB 539"],"award-info":[{"award-number":["SFB 539"]}]},{"name":"I2KF Erlangen","award":["B22"],"award-info":[{"award-number":["B22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Developmental Dynamics"],"published-print":{"date-parts":[[2002,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Previous experiments showed that transgenic mice expressing a secreted self\u2010activating transforming growth factor (TGF) \u2010\u03b21 did not show a phenotype in the lens and cornea until postnatal day 21, when anterior subcapsular cataracts, sporadic thickening of the corneal stroma, and thinning of the corneal epithelium were noted (Srinivasan et al., ). To examine the effects of higher concentrations of TGF\u2010\u03b21 on the lens and cornea, we constructed transgenic mice harboring the strong, lens\u2010specific chicken \u03b2B1\u2010crystallin promoter driving an activated porcine TGF\u2010\u03b21 gene. In contrast to the earlier study, the transgenic mice had microphthalmic eyes with closed eyelids. Already at embryonic day (E) 13.5, the future cornea of the transgenic mice was threefold thicker than that of wild\u2010type littermates due to increased proliferation of corneal stromal mesenchyme cells. Staining of fibronectin and thrombospondin\u20101 was increased in periocular mesenchyme. At E17.5, the thickened transgenic corneal stroma was vascularized and densely populated by abundant star\u2010shaped, neural cell adhesion molecule\u2013positive cells of mesenchymal appearance surrounded by irregular swirls of collagen and extracellular matrix. The corneal endothelium, anterior chamber, and stroma of iris\/ciliary body did not develop, and the transgenic cornea was opaque. Fibronectin, perlecan, and thrombospondin\u20101 were elevated, whereas type VI collagen decreased in the transgenic corneal stroma. Stromal mesenchyme cells expressed \u03b1\u2010smooth muscle actin as did lens epithelial cells and cells of the retinal pigmented epithelium. By E17.5, lens fiber cells underwent apoptotic cell death that was followed by apoptosis of the entire anterior lens epithelium between E18.5 and birth. Posteriorly, the vitreous humor was essentially absent; however, the retina appeared relatively normal. Thus, excess TGF\u2010\u03b21, a mitogen for embryonic corneal mesenchyme, severely disrupts corneal and lens differentiation. Our findings profoundly contrast with the mild eye phenotype observed with presumably lower levels of ectopic TGF\u2010\u03b2 and illustrate the complexity of TGF\u2010\u03b2 utilization and the importance of dose when assessing the effects of this growth factor. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/dvdy.10144","type":"journal-article","created":{"date-parts":[[2002,10,8]],"date-time":"2002-10-08T22:46:26Z","timestamp":1034117186000},"page":"111-125","source":"Crossref","is-referenced-by-count":57,"title":["Disruption of anterior segment development by TGF\u2010\u03b21 overexpression in the eyes of transgenic mice"],"prefix":"10.1002","volume":"225","author":[{"given":"Cassandra","family":"Fl\u00fcgel\u2010Koch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Ohlmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joram","family":"Piatigorsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst R.","family":"Tamm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,8,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713688609015099"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1364\/AO.10.000459"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1993.1026"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"13660","DOI":"10.1016\/S0021-9258(18)80047-3","article-title":"Site\u2010directed mutagenesis of cysteine residues in the pro region of the transforming growth factor \u03b21 precursor","volume":"264","author":"Brunner AM","year":"1989","journal-title":"J Biol Chem"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(01)00201-9"},{"key":"e_1_2_6_7_1","first-page":"1096","article-title":"Immunolocalization of type VI collagen in developing and healing rabbit cornea","volume":"31","author":"Cho HI","year":"1990","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.1242\/dev.121.12.4383","article-title":"FGF suppresses apoptosis and induces differentiation of fibre cells in the mouse lens","volume":"121","author":"Chow RL","year":"1995","journal-title":"Development"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713688408997237"},{"key":"e_1_2_6_10_1","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1242\/dev.128.20.3995","article-title":"Requirement for TGFbeta receptor signaling during terminal lens fiber differentiation","volume":"128","author":"de Iongh RU","year":"2001","journal-title":"Development"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1996.0033"},{"key":"e_1_2_6_12_1","first-page":"381","article-title":"Comparative embryologic studies of the early development of the cornea and the pupillary membrane in reptiles, birds and mammals","volume":"76","author":"Dublin I","year":"1970","journal-title":"Acta Anat (Basel)"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/33.7.2409130"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4781(94)00223-P"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4773(96)00533-3"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.126.17.3781"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9936"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713689409015091"},{"key":"e_1_2_6_19_1","first-page":"3231","article-title":"Intravitreal injection of TGFbeta induces cataract in rats","volume":"40","author":"Hales AM","year":"1999","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_20_1","first-page":"547","article-title":"Biosynthesis of stromal matrix proteoglycans and basement membrane components by human corneal fibroblasts","volume":"33","author":"Hassell JR","year":"1992","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)61760-X"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.105.6.2861"},{"key":"e_1_2_6_23_1","first-page":"168A","article-title":"Formaldehyde\u2010glutaraldehyde fixatives containing trinitro compounds","volume":"39","author":"Ito S","year":"1968","journal-title":"J Cell Biol"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199609000-00011"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199703000-00010"},{"issue":"5","key":"e_1_2_6_26_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1242\/jcs.112.5.613","article-title":"The cellular basis of corneal transparency: evidence for \u2018corneal crystallins\u2019","volume":"112","author":"Jester JV","year":"1999","journal-title":"J Cell Sci"},{"key":"e_1_2_6_27_1","first-page":"809","article-title":"Expression of alpha\u2010smooth muscle (alpha\u2010SM) actin during corneal stromal wound healing","volume":"36","author":"Jester JV","year":"1995","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(79)90164-7"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.5.1095"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.17.3.286.5212"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9314"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(79)90313-0"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511897948"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/neu.480260404"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1076\/ejom.34.4.295.13045"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.16.3.222.15408"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.1.239"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.67.1.753"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1957.sp005758"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.115.1.133"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(99)00029-5"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713689308995765"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713689408999890"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.23.7815"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091680109"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.115.4.1091"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.4.1105"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00365-8"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00187134"},{"key":"e_1_2_6_50_1","first-page":"2018","article-title":"Myofibroblast transformation of cat corneal endothelium by transforming growth factor\u2010beta1, \u2010beta2, and \u2010beta3","volume":"39","author":"Petroll WM","year":"1998","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041410221"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2000.0946"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1996.0328"},{"key":"e_1_2_6_54_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1242\/dev.127.3.533","article-title":"Formation of corneal endothelium is essential for anterior segment development","volume":"127","author":"Reneker LW","year":"2000","journal-title":"Development"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.12.3959"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(92)90226-7"},{"key":"e_1_2_6_57_1","first-page":"S659","article-title":"TGF\u03b22 involves in corneal morphogenesis during mouse embryonic development","volume":"42","author":"Saika S","year":"2001","journal-title":"Invest Ophthalmol Vis Sci (ARVO abstracts)"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.13.2659"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4781(95)00202-2"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.4.1599"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.111.1.117"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81112-5"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041400209"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1360"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1998.0540"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1996.0044"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199904)214:4<312::AID-AJA4>3.0.CO;2-A"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(91)90017-9"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(90)90008-7"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199703)208:3<375::AID-AJA8>3.0.CO;2-F"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0360"},{"key":"e_1_2_6_72_1","first-page":"1668","article-title":"Biosynthetic responses of the rabbit cornea to a keratectomy wound","volume":"28","author":"Zieske JD","year":"1987","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(86)80297-6"}],"container-title":["Developmental Dynamics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fdvdy.10144","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dvdy.10144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T20:31:25Z","timestamp":1760387485000},"score":1,"resource":{"primary":{"URL":"https:\/\/anatomypubs.onlinelibrary.wiley.com\/doi\/10.1002\/dvdy.10144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,8,28]]},"references-count":72,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002,10]]}},"alternative-id":["10.1002\/dvdy.10144"],"URL":"https:\/\/doi.org\/10.1002\/dvdy.10144","archive":["Portico"],"relation":{},"ISSN":["1058-8388","1097-0177"],"issn-type":[{"value":"1058-8388","type":"print"},{"value":"1097-0177","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,8,28]]}}}