Pax6 Regulation of Math5 During Mouse Retinal Neurogenesis

Overview

Journal Genesis

Specialties Biology
Molecular Biology

Date 2009 Feb 12

PMID 19208436

Citations 45

Authors

Amy N Riesenberg

Tien T Le

Minde I Willardsen

David C Blackburn

Monica L Vetter

Nadean L Brown

Affiliations

Soon will be listed here.

Abstract

Activation of the bHLH factor Math5 (Atoh7) is an initiating event for mammalian retinal neurogenesis, as it is critically required for retinal ganglion cell formation. However, the cis-regulatory elements and trans-acting factors that control Math5 expression are largely unknown. Using a combination of transgenic mice and bioinformatics, we identified a phylogenetically conserved regulatory element that is required to activate Math5 transcription during early retinal neurogenesis. This element drives retinal expression in vivo, in a cross-species transgenic assay. Previously, Pax6 was shown to be necessary for the initiation of Math5 mRNA expression. We extend this finding by showing that the Math5 retinal enhancer also requires Pax6 for its activation, via Pax6 binding to a highly conserved binding site. In addition, our data reveal that other retinal factors are required for accurate regulation of Math5 by Pax6.

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References

Cayouette M, Poggi L, Harris W . Lineage in the vertebrate retina. Trends Neurosci. 2006; 29(10):563-70. DOI: 10.1016/j.tins.2006.08.003. View

Inoue T, Hojo M, Bessho Y, Tano Y, Lee J, Kageyama R . Math3 and NeuroD regulate amacrine cell fate specification in the retina. Development. 2002; 129(4):831-42. DOI: 10.1242/dev.129.4.831. View

Epstein J, Glaser T, Cai J, Jepeal L, Walton D, Maas R . Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing. Genes Dev. 1994; 8(17):2022-34. DOI: 10.1101/gad.8.17.2022. View

Ovcharenko I, Loots G, Giardine B, Hou M, Ma J, Hardison R . Mulan: multiple-sequence local alignment and visualization for studying function and evolution. Genome Res. 2004; 15(1):184-94. PMC: 540288. DOI: 10.1101/gr.3007205. View

Turner D, Weintraub H . Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate. Genes Dev. 1994; 8(12):1434-47. DOI: 10.1101/gad.8.12.1434. View

Epstein J, Cai J, Glaser T, Jepeal L, Maas R . Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conformational changes. J Biol Chem. 1994; 269(11):8355-61. View

Roth H, Das G, Piatigorsky J . Chicken beta B1-crystallin gene expression: presence of conserved functional polyomavirus enhancer-like and octamer binding-like promoter elements found in non-lens genes. Mol Cell Biol. 1991; 11(3):1488-99. PMC: 369431. DOI: 10.1128/mcb.11.3.1488-1499.1991. View

Wang Y, Dakubo G, Thurig S, Mazerolle C, Wallace V . Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development. 2005; 132(22):5103-13. DOI: 10.1242/dev.02096. View

Marquardt T . Transcriptional control of neuronal diversification in the retina. Prog Retin Eye Res. 2003; 22(5):567-77. DOI: 10.1016/s1350-9462(03)00036-3. View

10.

Mu X, Klein W . A gene regulatory hierarchy for retinal ganglion cell specification and differentiation. Semin Cell Dev Biol. 2004; 15(1):115-23. DOI: 10.1016/j.semcdb.2003.09.009. View

11.

Hutcheson D, Vetter M . Transgenic approaches to retinal development and function in Xenopus laevis. Methods. 2003; 28(4):402-10. DOI: 10.1016/s1046-2023(02)00259-1. View

12.

Dyer M, Bremner R . The search for the retinoblastoma cell of origin. Nat Rev Cancer. 2005; 5(2):91-101. DOI: 10.1038/nrc1545. View

13.

Marquardt T, Ashery-Padan R, Andrejewski N, Scardigli R, Guillemot F, Gruss P . Pax6 is required for the multipotent state of retinal progenitor cells. Cell. 2001; 105(1):43-55. DOI: 10.1016/s0092-8674(01)00295-1. View

14.

Duncan M, Li X, Ogino H, Yasuda K, Piatigorsky J . Developmental regulation of the chicken beta B1-crystallin promoter in transgenic mice. Mech Dev. 1996; 57(1):79-89. DOI: 10.1016/0925-4773(96)00533-3. View

15.

Martinez-Morales J, Del Bene F, Nica G, Hammerschmidt M, Bovolenta P, Wittbrodt J . Differentiation of the vertebrate retina is coordinated by an FGF signaling center. Dev Cell. 2005; 8(4):565-74. DOI: 10.1016/j.devcel.2005.01.022. View

16.

Brown N, Patel S, Brzezinski J, Glaser T . Math5 is required for retinal ganglion cell and optic nerve formation. Development. 2001; 128(13):2497-508. PMC: 1480839. DOI: 10.1242/dev.128.13.2497. View

17.

Tucker P, Laemle L, Munson A, Kanekar S, Oliver E, Brown N . The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene. Genesis. 2001; 31(1):43-53. DOI: 10.1002/gene.10003. View

18.

Le T, Wroblewski E, Patel S, Riesenberg A, Brown N . Math5 is required for both early retinal neuron differentiation and cell cycle progression. Dev Biol. 2006; 295(2):764-78. DOI: 10.1016/j.ydbio.2006.03.055. View

19.

Skowronska-Krawczyk D, Ballivet M, Dynlacht B, Matter J . Highly specific interactions between bHLH transcription factors and chromatin during retina development. Development. 2004; 131(18):4447-54. DOI: 10.1242/dev.01302. View

20.

Xu P, Zhang X, Heaney S, Yoon A, MICHELSON A, Maas R . Regulation of Pax6 expression is conserved between mice and flies. Development. 1998; 126(2):383-95. DOI: 10.1242/dev.126.2.383. View