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Requirement of the Mowat-Wilson Syndrome Gene Zeb2 in the Differentiation and Maintenance of Non-photoreceptor Cell Types During Retinal Development

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Abstract

Mutations in the human transcription factor gene ZEB2 cause Mowat-Wilson syndrome, a congenital disorder characterized by multiple and variable anomalies including microcephaly, Hirschsprung disease, intellectual disability, epilepsy, microphthalmia, retinal coloboma, and/or optic nerve hypoplasia. Zeb2 in mice is involved in patterning neural and lens epithelia, neural tube closure, as well as in the specification, differentiation and migration of neural crest cells and cortical neurons. At present, it is still unclear how Zeb2 mutations cause retinal coloboma, whether Zeb2 inactivation results in retinal degeneration, and whether Zeb2 is sufficient to promote the differentiation of different retinal cell types. Here, we show that during mouse retinal development, Zeb2 is expressed transiently in early retinal progenitors and in all non-photoreceptor cell types including bipolar, amacrine, horizontal, ganglion, and Müller glial cells. Its retina-specific ablation causes severe loss of all non-photoreceptor cell types, cell fate switch to photoreceptors by retinal progenitors, and elevated apoptosis, which lead to age-dependent retinal degeneration, optic nerve hypoplasia, synaptic connection defects, and impaired ERG (electroretinogram) responses. Moreover, overexpression of Zeb2 is sufficient to promote the fate of all non-photoreceptor cell types at the expense of photoreceptors. Together, our data not only suggest that Zeb2 is both necessary and sufficient for the differentiation of non-photoreceptor cell types while simultaneously inhibiting the photoreceptor cell fate by repressing transcription factor genes involved in photoreceptor specification and differentiation, but also reveal a necessity of Zeb2 in the long-term maintenance of retinal cell types. This work helps to decipher the etiology of retinal atrophy associated with Mowat-Wilson syndrome and hence will impact on clinical diagnosis and management of the patients suffering from this syndrome.

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References

  1. Livesey FJ, Cepko CL (2001) Vertebrate neural cell-fate determination: lessons from the retina. Nat Rev Neurosci 2(2):109–118

    Article  CAS  PubMed  Google Scholar 

  2. Harris WA (1997) Cellular diversification in the vertebrate retina. Curr Opin Genet Dev 7(5):651–658

    Article  CAS  PubMed  Google Scholar 

  3. Xiang M (2013) Intrinsic control of mammalian retinogenesis. Cell Mol Life Sci 70(14):2519–2532. https://doi.org/10.1007/s00018-012-1183-2

    Article  CAS  PubMed  Google Scholar 

  4. Yang XJ (2004) Roles of cell-extrinsic growth factors in vertebrate eye pattern formation and retinogenesis. Semin Cell Dev Biol 15(1):91–103. https://doi.org/10.1016/j.semcdb.2003.09.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Boije H, MacDonald RB, Harris WA (2014) Reconciling competence and transcriptional hierarchies with stochasticity in retinal lineages. Curr Opin Neurobiol 27:68–74. https://doi.org/10.1016/j.conb.2014.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Agathocleous M, Harris WA (2009) From progenitors to differentiated cells in the vertebrate retina. Annu Rev Cell Dev Biol 25:45–69. https://doi.org/10.1146/annurev.cellbio.042308.113259

    Article  CAS  PubMed  Google Scholar 

  7. Swaroop A, Kim D, Forrest D (2010) Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina. Nat Rev Neurosci 11(8):563–576. https://doi.org/10.1038/nrn2880

    Article  CAS  PubMed  Google Scholar 

  8. Cronin T, Leveillard T, Sahel JA (2007) Retinal degenerations: from cell signaling to cell therapy; pre-clinical and clinical issues. Curr Gene Ther 7(2):121–129

    Article  CAS  PubMed  Google Scholar 

  9. Fitzpatrick DR, van Heyningen V (2005) Developmental eye disorders. Curr Opin Genet Dev 15(3):348–353. https://doi.org/10.1016/j.gde.2005.04.013

    Article  CAS  PubMed  Google Scholar 

  10. Zagozewski JL, Zhang Q, Eisenstat DD (2014) Genetic regulation of vertebrate eye development. Clin Genet 86(5):453–460. https://doi.org/10.1111/cge.12493

    Article  CAS  PubMed  Google Scholar 

  11. Espinosa-Parrilla Y, Amiel J, Auge J, Encha-Razavi F, Munnich A, Lyonnet S, Vekemans M, Attie-Bitach T (2002) Expression of the SMADIP1 gene during early human development. Mech Dev 114(1–2):187–191

    Article  CAS  PubMed  Google Scholar 

  12. Verschueren K, Remacle JE, Collart C, Kraft H, Baker BS, Tylzanowski P, Nelles L, Wuytens G et al (1999) SIP1, a novel zinc finger/homeodomain repressor, interacts with Smad proteins and binds to 5'-CACCT sequences in candidate target genes. J Biol Chem 274(29):20489–20498

    Article  CAS  PubMed  Google Scholar 

  13. Postigo AA, Dean DC (2000) Differential expression and function of members of the zfh-1 family of zinc finger/homeodomain repressors. Proc Natl Acad Sci U S A 97(12):6391–6396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yamada Y, Nomura N, Yamada K, Matsuo M, Suzuki Y, Sameshima K, Kimura R, Yamamoto Y et al (2014) The spectrum of ZEB2 mutations causing the Mowat-Wilson syndrome in Japanese populations. Am J Med Genet A 164A(8):1899–1908. https://doi.org/10.1002/ajmg.a.36551

    Article  CAS  PubMed  Google Scholar 

  15. Wenger TL, Harr M, Ricciardi S, Bhoj E, Santani A, Adam MP, Barnett SS, Ganetzky R et al (2014) CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases. Am J Med Genet A 164A(10):2557–2566. https://doi.org/10.1002/ajmg.a.36696

    Article  CAS  PubMed  Google Scholar 

  16. Ghoumid J, Drevillon L, Alavi-Naini SM, Bondurand N, Rio M, Briand-Suleau A, Nasser M, Goodwin L et al (2013) ZEB2 zinc-finger missense mutations lead to hypomorphic alleles and a mild Mowat-Wilson syndrome. Hum Mol Genet 22(13):2652–2661. https://doi.org/10.1093/hmg/ddt114

    Article  CAS  PubMed  Google Scholar 

  17. Garavelli L, Mainardi PC (2007) Mowat-Wilson syndrome. Orphanet J Rare Dis 2:42. https://doi.org/10.1186/1750-1172-2-42

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zweier C, Thiel CT, Dufke A, Crow YJ, Meinecke P, Suri M, Ala-Mello S, Beemer F et al (2005) Clinical and mutational spectrum of Mowat-Wilson syndrome. Eur J Med Genet 48(2):97–111. https://doi.org/10.1016/j.ejmg.2005.01.003

    Article  PubMed  Google Scholar 

  19. Wakamatsu N, Yamada Y, Yamada K, Ono T, Nomura N, Taniguchi H, Kitoh H, Mutoh N et al (2001) Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease. Nat Genet 27(4):369–370. https://doi.org/10.1038/86860

    Article  CAS  PubMed  Google Scholar 

  20. Gregory-Evans CY, Vieira H, Dalton R, Adams GG, Salt A, Gregory-Evans K (2004) Ocular coloboma and high myopia with Hirschsprung disease associated with a novel ZFHX1B missense mutation and trisomy 21. Am J Med Genet A 131(1):86–90. https://doi.org/10.1002/ajmg.a.30312

    Article  CAS  PubMed  Google Scholar 

  21. Tanteles GA, Christophidou-Anastasiadou V (2014) Ocular phenotype of Mowat-Wilson syndrome in the first reported Cypriot patients: an under-recognized association. Clin Dysmorphol 23(1):20–23. https://doi.org/10.1097/MCD.0000000000000013

    Article  PubMed  Google Scholar 

  22. Ariss M, Natan K, Friedman N, Traboulsi EI (2012) Ophthalmologic abnormalities in Mowat-Wilson syndrome and a mutation in ZEB2. Ophthalmic Genet 33(3):159–160. https://doi.org/10.3109/13816810.2011.610860

    Article  CAS  PubMed  Google Scholar 

  23. Dastot-Le Moal F, Wilson M, Mowat D, Collot N, Niel F, Goossens M (2007) ZFHX1B mutations in patients with Mowat-Wilson syndrome. Hum Mutat 28(4):313–321. https://doi.org/10.1002/humu.20452

    Article  CAS  PubMed  Google Scholar 

  24. McGaughran J, Sinnott S, Dastot-Le Moal F, Wilson M, Mowat D, Sutton B, Goossens M (2005) Recurrence of Mowat-Wilson syndrome in siblings with the same proven mutation. Am J Med Genet A 137A(3):302–304. https://doi.org/10.1002/ajmg.a.30896

    Article  PubMed  Google Scholar 

  25. Hurst JA, Markiewicz M, Kumar D, Brett EM (1988) Unknown syndrome: Hirschsprung’s disease, microcephaly, and iris coloboma: a new syndrome of defective neuronal migration. J Med Genet 25(7):494–497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Khor CC, Miyake M, Chen LJ, Shi Y, Barathi VA, Qiao F, Nakata I, Yamashiro K et al (2013) Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia. Hum Mol Genet 22(25):5288–5294. https://doi.org/10.1093/hmg/ddt385

    Article  CAS  PubMed  Google Scholar 

  27. Miquelajauregui A, Van de Putte T, Polyakov A, Nityanandam A, Boppana S, Seuntjens E, Karabinos A, Higashi Y et al (2007) Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation. Proc Natl Acad Sci U S A 104(31):12919–12924. https://doi.org/10.1073/pnas.0609863104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Van de Putte T, Maruhashi M, Francis A, Nelles L, Kondoh H, Huylebroeck D, Higashi Y (2003) Mice lacking ZFHX1B, the gene that codes for Smad-interacting protein-1, reveal a role for multiple neural crest cell defects in the etiology of Hirschsprung disease-mental retardation syndrome. Am J Hum Genet 72(2):465–470. https://doi.org/10.1086/346092

    Article  PubMed  PubMed Central  Google Scholar 

  29. Yoshimoto A, Saigou Y, Higashi Y, Kondoh H (2005) Regulation of ocular lens development by Smad-interacting protein 1 involving Foxe3 activation. Development 132(20):4437–4448. https://doi.org/10.1242/dev.02022

    Article  CAS  PubMed  Google Scholar 

  30. Seuntjens E, Nityanandam A, Miquelajauregui A, Debruyn J, Stryjewska A, Goebbels S, Nave KA, Huylebroeck D et al (2009) Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors. Nat Neurosci 12(11):1373–1380. https://doi.org/10.1038/nn.2409

    Article  CAS  PubMed  Google Scholar 

  31. van den Berghe V, Stappers E, Vandesande B, Dimidschstein J, Kroes R, Francis A, Conidi A, Lesage F et al (2013) Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1. Neuron 77(1):70–82. https://doi.org/10.1016/j.neuron.2012.11.009

    Article  CAS  PubMed  Google Scholar 

  32. Van de Putte T, Francis A, Nelles L, van Grunsven LA, Huylebroeck D (2007) Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat-Wilson syndrome. Hum Mol Genet 16(12):1423–1436. https://doi.org/10.1093/hmg/ddm093

    Article  CAS  PubMed  Google Scholar 

  33. Menuchin-Lasowski Y, Oren-Giladi P, Xie Q, Ezra-Elia R, Ofri R, Peled-Hajaj S, Farhy C, Higashi Y et al (2016) Sip1 regulates the generation of the inner nuclear layer retinal cell lineages in mammals. Development 143(15):2829–2841. https://doi.org/10.1242/dev.136101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Fujitani Y, Fujitani S, Luo H, Qiu F, Burlison J, Long Q, Kawaguchi Y, Edlund H et al (2006) Ptf1a determines horizontal and amacrine cell fates during mouse retinal development. Development 133(22):4439–4450

    Article  CAS  PubMed  Google Scholar 

  35. Li S, Mo Z, Yang X, Price SM, Shen MM, Xiang M (2004) Foxn4 controls the genesis of amacrine and horizontal cells by retinal progenitors. Neuron 43(6):795–807

    Article  CAS  PubMed  Google Scholar 

  36. Jin K, Jiang H, Xiao D, Zou M, Zhu J, Xiang M (2015) Tfap2a and 2b act downstream of Ptf1a to promote amacrine cell differentiation during retinogenesis. Mol Brain 8:28. https://doi.org/10.1186/s13041-015-0118-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Watanabe S, Sanuki R, Sugita Y, Imai W, Yamazaki R, Kozuka T, Ohsuga M, Furukawa T (2015) Prdm13 regulates subtype specification of retinal amacrine interneurons and modulates visual sensitivity. J Neurosci 35(20):8004–8020. https://doi.org/10.1523/JNEUROSCI.0089-15.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Higashi Y, Maruhashi M, Nelles L, Van de Putte T, Verschueren K, Miyoshi T, Yoshimoto A, Kondoh H et al (2002) Generation of the floxed allele of the SIP1 (Smad-interacting protein 1) gene for Cre-mediated conditional knockout in the mouse. Genesis 32(2):82–84

    Article  CAS  PubMed  Google Scholar 

  39. Furuta Y, Lagutin O, Hogan BL, Oliver GC (2000) Retina- and ventral forebrain-specific Cre recombinase activity in transgenic mice. Genesis 26(2):130–132. https://doi.org/10.1002/(SICI)1526-968X(200002)26:2<130::AID-GENE9>3.0.CO;2-I

    Article  CAS  PubMed  Google Scholar 

  40. Qiu F, Jiang H, Xiang M (2008) A comprehensive negative regulatory program controlled by Brn3b to ensure ganglion cell specification from multipotential retinal precursors. J Neurosci 28(13):3392–3403. https://doi.org/10.1523/JNEUROSCI.0043-08.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kawaguchi Y, Cooper B, Gannon M, Ray M, MacDonald RJ, Wright CV (2002) The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat Genet 32(1):128–134. https://doi.org/10.1038/ng959

    Article  CAS  PubMed  Google Scholar 

  42. Li C, Wong WH (2003) DNA-Chip analyzer (dChip). In: Parmigiani G, Garrett ES, Irizarry R, Zeger SL (eds) The analysis of gene expression data: methods and software. Springer-Verlag, New York, pp. 120–141

    Chapter  Google Scholar 

  43. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL et al (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102(43):15545–15550. https://doi.org/10.1073/pnas.0506580102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, Christmas R, Avila-Campilo I et al (2007) Integration of biological networks and gene expression data using Cytoscape. Nat Protoc 2(10):2366–2382. https://doi.org/10.1038/nprot.2007.324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Merico D, Isserlin R, Stueker O, Emili A, Bader GD (2010) Enrichment map: a network-based method for gene-set enrichment visualization and interpretation. PLoS One 5(11):e13984. https://doi.org/10.1371/journal.pone.0013984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sciavolino PJ, Abrams EW, Yang L, Austenberg LP, Shen MM, Abate-Shen C (1997) Tissue-specific expression of murine Nkx3.1 in the male urogenital system. Dev Dyn 209(1):127–138

    Article  CAS  PubMed  Google Scholar 

  47. Mo Z, Li S, Yang X, Xiang M (2004) Role of the Barhl2 homeobox gene in the specification of glycinergic amacrine cells. Development 131(7):1607–1618

    Article  CAS  PubMed  Google Scholar 

  48. Hodges RS, Heaton RJ, Parker JM, Molday L, Molday RS (1988) Antigen-antibody interaction. Synthetic peptides define linear antigenic determinants recognized by monoclonal antibodies directed to the cytoplasmic carboxyl terminus of rhodopsin. J Biol Chem 263(24):11768–11775

    CAS  PubMed  Google Scholar 

  49. Yang S, Luo X, Xiong G, So KF, Yang H, Xu Y (2015) The electroretinogram of Mongolian gerbil (Meriones unguiculatus): comparison to mouse. Neurosci Lett 589:7–12. https://doi.org/10.1016/j.neulet.2015.01.018

    Article  CAS  PubMed  Google Scholar 

  50. Wu XH, Qian KW, Xu GZ, Li YY, Ma YY, Huang F, Wang YQ, Zhou X et al (2016) The role of retinal dopamine in C57BL/6 mouse refractive development as revealed by intravitreal administration of 6-hydroxydopamine. Invest Ophthalmol Vis Sci 57(13):5393–5404. https://doi.org/10.1167/iovs.16-19543

    Article  CAS  PubMed  Google Scholar 

  51. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Irie S, Sanuki R, Muranishi Y, Kato K, Chaya T, Furukawa T (2015) Rax homeoprotein regulates photoreceptor cell maturation and survival in association with Crx in the postnatal mouse retina. Mol Cell Biol 35(15):2583–2596. https://doi.org/10.1128/MCB.00048-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Mansergh FC, Carrigan M, Hokamp K, Farrar GJ (2015) Gene expression changes during retinal development and rod specification. Mol Vis 21:61–87

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Megason SG, McMahon AP (2002) A mitogen gradient of dorsal midline Wnts organizes growth in the CNS. Development 129(9):2087–2098

    CAS  PubMed  Google Scholar 

  55. Jin K, Jiang H, Mo Z, Xiang M (2010) Early B-cell factors are required for specifying multiple retinal cell types and subtypes from postmitotic precursors. J Neurosci 30(36):11902–11916. https://doi.org/10.1523/JNEUROSCI.2187-10.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kuwajima T, Soares CA, Sitko AA, Lefebvre V, Mason C (2017) SoxC transcription factors promote contralateral retinal ganglion cell differentiation and axon guidance in the mouse visual system. Neuron 93(5):1110–1125 e1115. https://doi.org/10.1016/j.neuron.2017.01.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Petros TJ, Shrestha BR, Mason C (2009) Specificity and sufficiency of EphB1 in driving the ipsilateral retinal projection. J Neurosci 29(11):3463–3474. https://doi.org/10.1523/JNEUROSCI.5655-08.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Jin K, Xiang M (2012) In vitro explant culture and related protocols for the study of mouse retinal development. Methods Mol Biol 884:155–165. https://doi.org/10.1007/978-1-61779-848-1_10

    Article  CAS  PubMed  Google Scholar 

  59. Dick E, Miller RF (1985) Extracellular K+ activity changes related to electroretinogram components. I. Amphibian (I-type) retinas. J Gen Physiol 85(6):885–909

    Article  CAS  PubMed  Google Scholar 

  60. Stockton RA, Slaughter MM (1989) B-wave of the electroretinogram. A reflection of ON bipolar cell activity. J Gen Physiol 93(1):101–122

    Article  CAS  PubMed  Google Scholar 

  61. Robson JG, Maeda H, Saszik SM, Frishman LJ (2004) In vivo studies of signaling in rod pathways of the mouse using the electroretinogram. Vis Res 44(28):3253–3268. https://doi.org/10.1016/j.visres.2004.09.002

    Article  CAS  PubMed  Google Scholar 

  62. Mears AJ, Kondo M, Swain PK, Takada Y, Bush RA, Saunders TL, Sieving PA, Swaroop A (2001) Nrl is required for rod photoreceptor development. Nat Genet 29(4):447–452

    Article  CAS  PubMed  Google Scholar 

  63. Furukawa T, Morrow EM, Cepko CL (1997) Crx, a novel otx-like homeobox gene, shows photoreceptor-specific expression and regulates photoreceptor differentiation. Cell 91(4):531–541

    Article  CAS  PubMed  Google Scholar 

  64. Chen J, Rattner A, Nathans J (2005) The rod photoreceptor-specific nuclear receptor Nr2e3 represses transcription of multiple cone-specific genes. J Neurosci 25(1):118–129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Corbo JC, Cepko CL (2005) A hybrid photoreceptor expressing both rod and cone genes in a mouse model of enhanced S-cone syndrome. PLoS Genet 1(2):e11

    Article  PubMed  PubMed Central  Google Scholar 

  66. Peng GH, Ahmad O, Ahmad F, Liu J, Chen S (2005) The photoreceptor-specific nuclear receptor Nr2e3 interacts with Crx and exerts opposing effects on the transcription of rod versus cone genes. Hum Mol Genet 14(6):747–764

    Article  CAS  PubMed  Google Scholar 

  67. Misra K, Luo H, Li S, Matise M, Xiang M (2014) Asymmetric activation of Dll4-notch signaling by Foxn4 and proneural factors activates BMP/TGFbeta signaling to specify V2b interneurons in the spinal cord. Development 141(1):187–198. https://doi.org/10.1242/dev.092536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wu F, Li R, Umino Y, Kaczynski TJ, Sapkota D, Li S, Xiang M, Fliesler SJ, Sherry DM, Gannon M, Solessio E, Mu X (2013) Onecut1 is essential for horizontal cell genesis and retinal integrity. J Neurosci 33 (32):13053–13065, 13065a. https://doi.org/10.1523/JNEUROSCI.0116-13.2013

  69. Keeley PW, Luna G, Fariss RN, Skyles KA, Madsen NR, Raven MA, Poche RA, Swindell EC et al (2013) Development and plasticity of outer retinal circuitry following genetic removal of horizontal cells. J Neurosci 33(45):17847–17862. https://doi.org/10.1523/JNEUROSCI.1373-13.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Sonntag S, Dedek K, Dorgau B, Schultz K, Schmidt KF, Cimiotti K, Weiler R, Lowel S et al (2012) Ablation of retinal horizontal cells from adult mice leads to rod degeneration and remodeling in the outer retina. J Neurosci 32(31):10713–10724. https://doi.org/10.1523/JNEUROSCI.0442-12.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Drs. Chuang Shen and Shuting Liu for critical reading of and thoughtful comments on the manuscript. This work was supported in part by the National Key R&D Program of China (2017YFA0104100), National Basic Research Program (973 Program) of China (2015CB964600), National Natural Science Foundation of China (81670862), Science and Technology Planning Projects of Guangdong Province (2017B030314025), National Institutes of Health (EY020849 and EY012020), and the Fundamental Research Funds of the State Key Laboratory of Ophthalmology, Sun Yat-sen University to MX.

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  1. Bin Liu

    Present address: Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, China

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  1. State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China

    Wen Wei, Bin Liu, Kangxin Jin & Mengqing Xiang

  2. Center for Advanced Biotechnology and Medicine and Department of Pediatrics, Rutgers University-Robert Wood Johnson Medical School, 679 Hoes Lane West, Piscataway, NJ, 08854, USA

    Haisong Jiang & Mengqing Xiang

  3. Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

    Mengqing Xiang

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Wei, W., Liu, B., Jiang, H. et al. Requirement of the Mowat-Wilson Syndrome Gene Zeb2 in the Differentiation and Maintenance of Non-photoreceptor Cell Types During Retinal Development. Mol Neurobiol 56, 1719–1736 (2019). https://doi.org/10.1007/s12035-018-1186-6

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