Sox9 is expressed in mouse multipotent retinal progenitor cells and functions in Müller Glial cell development

Poché, Ross A.; Furuta, Yasuhide; Chaboissier, Marie-Christine; Schedl, Andreas; Behringer, Richard R.

doi:10.1002/cne.21746

Cited by 159 publications

(118 citation statements)

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“…Paired SOX Site Contributes to BEST1 Promoter Activity-Of the three SOX-E factors, it was reported that SOX9 is expressed in mouse RPE from embryonic stages through adults (19), raising the possibility that SOX9 might be the regulator of BEST1 in the RPE. Based on the reported findings that SOX9 regulates mouse Col11a2 and Ptgds through paired SOX sites (underlined) CACAAGGCGTGCTTTGTC in the enhancer (41) and CACAAATGGTGCTTTGTG in the promoter (46), respectively, we reanalyzed the sequence of Bait 6.…”

Section: Yoh Screen With Best1 Promoter Elements Identified Sox-ementioning

confidence: 99%

“…2C). As for the antibodies used, the specificity of the AB5535 antibody was previously demonstrated by immunohistochemistry of retinal sections in which SOX9 staining in Müller glia was abrogated in conditional Sox9 knock-out mice (19). The sc-17342 and ab25978 antibodies were both polyclonal and generated using human SOX10 peptides of 20 (N-terminal) and 50 (at 178 -227 amino acid position) amino acids, respectively (63,64).…”

Section: Sox9 Is Highly and Preferentially Expressed In Rpe-mentioning

confidence: 99%

mentioning

confidence: 99%

“…However, a number of questions remained to be answered. Recently, it has been found unintentionally that SRY (sex-determining region Y) box 9 (SOX9) is robustly expressed in mouse RPE throughout embryonic development and into postnatal stages (19).…”

mentioning

confidence: 99%

“…In mice, heterozygous Sox9 knockouts (Sox9 ϩ/Ϫ ) recapitulate most of the skeletal abnormalities of CD and die perinatally (36). In the eye, SOX9 expression has been found in mouse retinal progenitor cells and Müller glia (19,37), and conditional knock-out mice revealed the essential role of SOX9 in the differentiation and/or survival of postnatal Müller glia (19). In matured human skin, SOX9 is a key player in ultraviolet B radiation-induced melanocyte differentiation and pigmentation by directly regulating MITF (38).…”

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confidence: 99%

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SOX9, through Interaction with Microphthalmia-associated Transcription Factor (MITF) and OTX2, Regulates BEST1 Expression in the Retinal Pigment Epithelium

Masuda

Esumi

2010

Journal of Biological Chemistry

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BEST1 is highly and preferentially expressed in the retinal pigment epithelium (RPE) and causes Best macular dystrophy when mutated. We previously demonstrated that the human BEST1 upstream region ؊154 to ؉38 bp is sufficient to direct expression in the RPE of transgenic mice, and microphthalmiaassociated transcription factor (MITF) and OTX2 regulate this BEST1 promoter. However, a number of questions remained. Here, we show that yeast one-hybrid screen with bait corresponding to BEST1 ؊120 to ؊88 bp identified the SOX-E factors, SOX8, SOX9, and SOX10. A paired SOX site was found in this bait, and mutation of either of the paired sites significantly decreased BEST1 promoter activity in RPE primary cultures. Among the SOX-E genes, SOX9 is highly and preferentially expressed in the RPE, and chromatin immunoprecipitation with fresh RPE cells revealed binding of SOX9, but not SOX10, to the BEST1 region where the paired SOX site is located. BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. Importantly, SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles. A combination of the expression patterns of SOX9, MITF, and OTX2 yielded tissue distribution remarkably similar to that of BEST1. Lastly, the BEST1 promoter was also active in Sertoli cells of the testis in transgenic mice where SOX9 is highly expressed. These results define SOX9 as a key regulator of BEST1 expression and demonstrate for the first time its functional role in the RPE. The retinal pigment epithelium (RPE)2 has many specialized functions essential for vision and is indispensable for the survival and function of retinal photoreceptors (1, 2). RPE cells and melanocytes, two major pigmented cells in the body, share pigment-related genes such as tyrosinase (Tyr) and dopachrome tautomerase (Dct) and transcription factors regulating them such as microphthalmia-associated transcription factor (MITF); otherwise, these two cell types are distinct in many aspects. Although the molecular networks controlling gene expression in melanocytes have been extensively studied (3, 4), those in the RPE are still poorly understood. Among the key transcription factors required for RPE specification and development are MITF (3-9) and orthodenticle homeobox 2 (OTX2) (10 -14). MITF and OTX2 proteins physically interact with each other and cooperatively activate some pigment-related genes in the RPE, such as QNR71 and Tyr (15). Our previous studies found that human BEST1, a gene that is highly and preferentially expressed in the RPE but not related to pigment, is also regulated by . However, a number of questions remained to be answered. Recently, it has been found unintentionally that SRY (sex-determining region Y) box 9 (SOX9) is robustly expressed in mouse RPE throughout embryonic development and into postnatal stages (19).SOX9 is a member of the SOX family of transcription factors, which is characterized by the hig...

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Section: Yoh Screen With Best1 Promoter Elements Identified Sox-ementioning

confidence: 99%

Section: Sox9 Is Highly and Preferentially Expressed In Rpe-mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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SOX9, through Interaction with Microphthalmia-associated Transcription Factor (MITF) and OTX2, Regulates BEST1 Expression in the Retinal Pigment Epithelium

Masuda

Esumi

2010

Journal of Biological Chemistry

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The capacity of neural crest‐derived stem cells for ocular repair

Liu

Hunter

Smith

et al. 2014

Birth Defects Research Pt C

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Whether it is due to a particular epigenetic signature, or some other component of an embryonic differentiation program, accumulating evidence indicates that the origins of a stem cell has a profound impact on the potential of a tissue to regenerate and repair. Here, we focus on Müller glia, long considered the stem cells of the retina, and their surprising derivation from the neural crest. Whether the multipotent properties of a subset of Müller glia is associated with their neural crest origin remains a tantalizing possibility.

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Comparative study of Pax2 expression in glial cells in the retina and optic nerve of birds and mammals

Stanke

Moose

El‐Hodiri

et al. 2010

J of Comparative Neurology

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Little is known about the expression of Pax2 in mature retina or optic nerve. Here we probed for the expression of Pax2 in late stages of embryonic development and in mature chick retina. We find two distinct Pax2 isoforms expressed by cells within the retina and optic nerve. Surprisingly, Müller glia in central regions of the retina express Pax2, and levels of expression are decreased with increasing distance from the nerve head. In Müller glia, the expression levels of Pax2 are increased by acute retinal damage or treatment with growth factors. At the optic nerve, Pax2 is expressed by peripapillary glia, at the junction of the neural retina and optic nerve head and by glia within the optic nerve. In addition, we assayed for Pax2 expression in glial cells in mammalian retinas. In mammalian retinas, unlike the case in chick retina, the Müller glia do not express Pax2. Pax2-expressing cells are found in the optic nerve and astrocytes within the mouse retina. By comparison, Pax2-positive cells are not found within the guinea pig retina; Pax2-expressing glia are confined to the optic nerve. In dog and monkey (Macaca fascicularis), Pax2 is expressed by astrocytes that are scattered across inner retinal layers and by numerous glia within the optic nerve. Interestingly, Pax2-positive glial cells are found at the peripheral edge of the dog retina, but only in older animals. We conclude that the expression of Pax2 in the vertebrate eye is restricted to retinal astrocytes, peripapillary glia, and glia within the optic nerve.

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Sox9 is expressed in mouse multipotent retinal progenitor cells and functions in Müller Glial cell development

Cited by 159 publications

References 68 publications

SOX9, through Interaction with Microphthalmia-associated Transcription Factor (MITF) and OTX2, Regulates BEST1 Expression in the Retinal Pigment Epithelium

SOX9, through Interaction with Microphthalmia-associated Transcription Factor (MITF) and OTX2, Regulates BEST1 Expression in the Retinal Pigment Epithelium

The capacity of neural crest‐derived stem cells for ocular repair

Comparative study of Pax2 expression in glial cells in the retina and optic nerve of birds and mammals

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