{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:24:26Z","timestamp":1792027466864,"version":"4.4.0"},"reference-count":73,"publisher":"The Company of Biologists","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,6,1]]},"abstract":"<jats:p>Patterning of the vertebrate eye appears to be controlled by the mutual regulation and the progressive restriction of the expression domains of a number of genes initially co-expressed within the eye anlage. Previous data suggest that both Otx1 and Otx2 might contribute to the establishment of the different eye territories. Here, we have analysed the ocular phenotype of mice carrying different functional copies of Otx1 and Otx2 and we show that these genes are required in a dose-dependent manner for the normal development of the eye. Thus, all Otx1\u2212\/\u2212; Otx2+\/\u2212 and 30% of Otx1+\/\u2212; Otx2+\/\u2212 genotypes presented consistent and profound ocular malformation, including lens, pigment epithelium, neural retina and optic stalk defects. During embryonic development, optic vesicle infolding was severely altered and the expression of pigment epithelium-specific genes, such as Mitf or tyrosinase, was lost. Lack of pigment epithelium specification was associated with an expansion of the prospective neural retina and optic stalk territories, as determined by the expression of Pax6, Six3 and Pax2. Later in development the presumptive pigment epithelium region acquired features of mature neural retina, including the generation of Islet1-positive neurones. Furthermore, in Otx1\u2212\/\u2212; Otx2+\/\u2212 mice neural retina cell proliferation, cell differentiation and apoptotic cell death were also severely affected. Based on these findings we propose a model in which Otx gene products are required for the determination and differentiation of the pigment epithelium, co-operating with other eye patterning genes in the determination of the specialised tissues that will constitute the mature vertebrate eye.<\/jats:p>","DOI":"10.1242\/dev.128.11.2019","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T05:51:07Z","timestamp":1619416267000},"page":"2019-2030","source":"Crossref","is-referenced-by-count":255,"title":["Otx genes are required for tissue specification in the developing eye"],"prefix":"10.1242","volume":"128","author":[{"given":"Juan Ramon","family":"Martinez-Morales","sequence":"first","affiliation":[{"name":"Instituto Cajal, CSIC, Dr Arce 37, Madrid 28002, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Signore","sequence":"additional","affiliation":[{"name":"MRC Centre for Developmental Neurobiology, New Hunt\u2019s House, 4th Floor, King\u2019s College London, Guy\u2019s Campus, London Bridge, London SE11 9RT, UK"},{"name":"International Institute of Genetics and Biophysics, CNR, Via Marconi, 12, 80125 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Acampora","sequence":"additional","affiliation":[{"name":"MRC Centre for Developmental Neurobiology, New Hunt\u2019s House, 4th Floor, King\u2019s College London, Guy\u2019s Campus, London Bridge, London SE11 9RT, UK"},{"name":"International Institute of Genetics and Biophysics, CNR, Via Marconi, 12, 80125 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Simeone","sequence":"additional","affiliation":[{"name":"MRC Centre for Developmental Neurobiology, New Hunt\u2019s House, 4th Floor, King\u2019s College London, Guy\u2019s Campus, London Bridge, London SE11 9RT, UK"},{"name":"International Institute of Genetics and Biophysics, CNR, Via Marconi, 12, 80125 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Bovolenta","sequence":"additional","affiliation":[{"name":"Instituto Cajal, CSIC, Dr Arce 37, Madrid 28002, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042604571468700_ACAMPORA-ETAL-1995","doi-asserted-by":"crossref","unstructured":"Acampora, D., Mazan, S., Lallemand, Y., Avantaggiato, V., Maury, M., Simeone, A. and Brulet, P. 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