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Open Access Highly Accessed Research article

Histone deacetylase expression patterns in developing murine optic nerve

Sarika Tiwari12, Subramanian Dharmarajan12, Mahesh Shivanna3, Deborah C Otteson4 and Teri L Belecky-Adams12*

Author Affiliations

1 Department of Biology, Center for Developmental and Regenerative Biology, Indiana University-Purdue University Indianapolis, 723 W Michigan St, Indianapolis IN-46202, India

2 Center for Regenerative Biology and Medicine, Indiana University-Purdue University Indianapolis, 723 W Michigan St, Indianapolis IN-46202, India

3 School of Optometry, MCPHS University, 10 Lincoln Sq., Worcester MA-01608, UK

4 University of Houston College of Optometry, 4901 Calhoun Rd, Houston, TX 77204-2020, USA

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BMC Developmental Biology 2014, 14:30  doi:10.1186/1471-213X-14-30

Published: 9 July 2014

Abstract

Background

Histone deacetylases (HDACs) play important roles in glial cell development and in disease states within multiple regions of the central nervous system. However, little is known about HDAC expression or function within the optic nerve. As a first step in understanding the role of HDACs in optic nerve, this study examines the spatio-temporal expression patterns of methylated histone 3 (K9), acetylated histone 3 (K18), and HDACs 1–6 and 8–11 in the developing murine optic nerve head.

Results

Using RT-qPCR, western blot and immunofluorescence, three stages were analyzed: embryonic day 16 (E16), when astrocyte precursors are found in the optic stalk, postnatal day 5 (P5), when immature astrocytes and oligodendrocytes are found throughout the optic nerve, and P30, when optic nerve astrocytes and oligodendrocytes are mature. Acetylated and methylated histone H3 immunoreactivity was co-localized in the nuclei of most SOX2 positive glia within the optic nerve head and adjacent optic nerve at all developmental stages. HDACs 1–11 were expressed in the optic nerve glial cells at all three stages of optic nerve development in the mouse, but showed temporal differences in overall levels and subcellular localization. HDACs 1 and 2 were predominantly nuclear throughout optic nerve development and glial cell maturation. HDACs 3, 5, 6, 8, and 11 were predominantly cytoplasmic, but showed nuclear localization in at least one stage of optic nerve development. HDACs 4, 9 and10 were predominantly cytoplasmic, with little to no nuclear expression at any time during the developmental stages examined.

Conclusions

Our results showing that HDACs 1, 2, 3, 5, 6, 8, and 11 were each localized to the nuclei of SOX2 positive glia at some stages of optic nerve development and maturation and extend previous reports of HDAC expression in the aging optic nerve. These HDACs are candidates for further research to understand how chromatin remodeling through acetylation, deacetylation and methylation contributes to glial development as well as their injury response.

Keywords:
Histone deacetylases; HDACs; Mouse; Murine; Development; Optic nerve; Optic stalk; Astrocytes; Astrocyte precursors; Glial lamina