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Biol Open. 2013 Sep 06;2(11):1125-36. doi: 10.1242/bio.20132279. eCollection 2013.

Meis1 regulates Foxn4 expression during retinal progenitor cell differentiation.

Biology open

Mohammed M Islam, Ying Li, Huijun Luo, Mengqing Xiang, Li Cai

Affiliations

  1. Department of Biomedical Engineering, Rutgers University , 599 Taylor Road, Piscataway, NJ 08854 , USA ; Present address: Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX 75390, USA.

PMID: 24244849 PMCID: PMC3828759 DOI: 10.1242/bio.20132279

Abstract

The transcription factor forkhead box N4 (Foxn4) is a key regulator in a variety of biological processes during development. In particular, Foxn4 plays an essential role in the genesis of horizontal and amacrine neurons from neural progenitors in the vertebrate retina. Although the functions of Foxn4 have been well established, the transcriptional regulation of Foxn4 expression during progenitor cell differentiation remains unclear. Here, we report that an evolutionarily conserved 129 bp noncoding DNA fragment (Foxn4CR4.2 or CR4.2), located ∼26 kb upstream of Foxn4 transcription start site, functions as a cis-element for Foxn4 regulation. CR4.2 directs gene expression in Foxn4-positive cells, primarily in progenitors, differentiating horizontal and amacrine cells. We further determined that the gene regulatory activity of CR4.2 is modulated by Meis1 binding motif, which is bound and activated by Meis1 transcription factor. Deletion of the Meis1 binding motif or knockdown of Meis1 expression abolishes the gene regulatory activity of CR4.2. In addition, knockdown of Meis1 expression diminishes the endogenous Foxn4 expression and affects cell lineage development. Together, we demonstrate that CR4.2 and its interacting Meis1 transcription factor play important roles in regulating Foxn4 expression during early retinogenesis. These findings provide new insights into molecular mechanisms that govern gene regulation in retinal progenitors and specific cell lineage development.

Keywords: Amacrine cell; Enhancer; Foxn4; Horizontal cell; Meis1; Retinal progenitor

References

  1. Dev Dyn. 2011 Jun;240(6):1512-7 - PubMed
  2. Mech Dev. 2001 Sep;107(1-2):203-6 - PubMed
  3. Genome Res. 2005 Aug;15(8):1061-72 - PubMed
  4. BMC Dev Biol. 2010 Jan 20;10:8 - PubMed
  5. Genes Dev. 1993 Jul;7(7A):1277-89 - PubMed
  6. Am J Hum Genet. 2005 Jan;76(1):8-32 - PubMed
  7. Science. 2006 Feb 10;311(5762):796-800 - PubMed
  8. Nature. 1994 Aug 18;370(6490):567-71 - PubMed
  9. Eur J Histochem. 2006 Apr-Jun;50(2):147-54 - PubMed
  10. Development. 1992 Sep;116(1):201-11 - PubMed
  11. Dev Biol. 2009 Jun 15;330(2):318-28 - PubMed
  12. J Vis Exp. 2009 Sep 24;(31): - PubMed
  13. Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W273-9 - PubMed
  14. Development. 2002 Feb;129(4):831-42 - PubMed
  15. Mol Cell Biol. 2006 Aug;26(15):5650-62 - PubMed
  16. Development. 2006 Oct;133(20):4085-96 - PubMed
  17. Methods Mol Biol. 2000;132:337-49 - PubMed
  18. Development. 2000 Aug;127(15):3237-47 - PubMed
  19. Development. 2006 Nov;133(22):4439-50 - PubMed
  20. Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):16-22 - PubMed
  21. Bioinformatics. 2005 Jul 1;21(13):2933-42 - PubMed
  22. Nucleic Acids Res. 1995 Dec 11;23(23):4878-84 - PubMed
  23. Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3860-8 - PubMed
  24. Science. 2006 Apr 14;312(5771):276-9 - PubMed
  25. Dev Biol. 2011 Dec 1;360(1):241-55 - PubMed
  26. Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W369-73 - PubMed
  27. Genes Dev. 2008 Mar 15;22(6):734-9 - PubMed
  28. Nat Commun. 2013;4:1813 - PubMed
  29. Gene Expr Patterns. 2007 Jan;7(3):233-8 - PubMed
  30. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1649-54 - PubMed
  31. Development. 2001 Jul;128(13):2421-32 - PubMed
  32. Brain Res Dev Brain Res. 2004 Oct 15;153(1):115-9 - PubMed
  33. Dev Biol. 2006 Apr 1;292(1):265-76 - PubMed
  34. Dev Biol. 2003 Dec 1;264(1):240-54 - PubMed
  35. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1684-8 - PubMed
  36. Neuron. 2004 Sep 16;43(6):795-807 - PubMed
  37. Development. 2001 Apr;128(8):1313-22 - PubMed
  38. Mol Cell Biol. 2004 May;24(10):4513-21 - PubMed
  39. Development. 2008 Mar;135(5):805-11 - PubMed
  40. J Biol Chem. 1996 Feb 2;271(5):2667-75 - PubMed
  41. Nat Rev Neurosci. 2001 Feb;2(2):109-18 - PubMed
  42. BMC Dev Biol. 2007 Jul 16;7:85 - PubMed
  43. Genome Res. 2006 Jul;16(7):855-63 - PubMed
  44. Neuron. 1990 Mar;4(3):469-76 - PubMed
  45. Neural Dev. 2010 Sep 01;5:22 - PubMed
  46. Dev Dyn. 1992 Dec;195(4):231-72 - PubMed
  47. Mech Dev. 2002 Oct;118(1-2):179-85 - PubMed
  48. Eur J Neurosci. 1991 Jun;3(6):559-569 - PubMed
  49. J Neurosci. 2008 Apr 9;28(15):3835-6 - PubMed
  50. Dev Dyn. 1992 Dec;195(4):273-5 - PubMed
  51. Methods Mol Biol. 2003;232:127-31 - PubMed
  52. Genome Res. 2007 Feb;17(2):201-11 - PubMed
  53. Neuron. 2009 Mar 26;61(6):852-64 - PubMed
  54. Anat Embryol (Berl). 1981;161(3):319-27 - PubMed
  55. Curr Opin Neurobiol. 2001 Aug;11(4):431-6 - PubMed
  56. Genome Res. 2003 Apr;13(4):721-31 - PubMed
  57. BMC Bioinformatics. 2007 Mar 15;8:94 - PubMed
  58. J Neurosci. 2007 Dec 19;27(51):14099-107 - PubMed
  59. Gene Expr Patterns. 2008 Jan;8(2):117-23 - PubMed
  60. J Vis Exp. 2012 Feb 05;(60): - PubMed
  61. Differentiation. 2013 Jan;85(1-2):11-9 - PubMed

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