Histone deacetylase expression patterns in developing murine optic nerve

Sarika Tiwari,Teri L Belecky-Adams,Deborah C Otteson,Subramanian Dharmarajan,Mahesh Shivanna

doi:10.1186/1471-213x-14-30

Abstract

BackgroundHistone 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.ResultsUsing 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.ConclusionsOur 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.

Highlights

Histone deacetylases (HDACs) play important roles in glial cell development and in disease states within multiple regions of the central nervous system
Three different stages of development were chosen for these studies; embryonic day 16 (E16), which is a period when astrocyte precursors are found in the nascent optic nerve, postnatal day 5 (P5) when immature astrocytes are found throughout the optic nerve, including the optic nerve head and developing lamina and P30 when the glia within the lamina, as well as the optic nerve astrocytes and oligodendrocytes are mature [26,27,28]
Sections through the optic nerve head and adjacent optic nerve were triple-labeled with antibodies against SOX2, which labels glia in the peripapillary, laminar and optic nerve regions, and antibodies against methylated histone H3 (MeH3K9) and acetylated histone H3 (AcH3K18) as markers of closed and open chromatin structure respectively

Summary

Introduction

Histone deacetylases (HDACs) play important roles in glial cell development and in disease states within multiple regions of the central nervous system. Astrocytes, once thought to be relatively inert cells, have been shown to play a multitude of roles in the developing, mature, and injured or diseased central nervous system [1,2]. Astrocytes play key roles in synaptogenesis, maintenance of ion and transmitter levels, metabolic homeostasis, and support of neurons following injury [3]. Little is known about the role that specific epigenetic factors play in the development of optic nerve glia

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