Abstract

In the developing central nervous system (CNS), progenitor cells differentiate into progeny to form functional neural circuits. Radial glial cells (RGs) are a transient progenitor cell type that is present during neurogenesis. It is thought that a combination of neural trophic factors, neurotransmitters and electrical activity regulates the proliferation and differentiation of RGs. However, it is less clear how epigenetic modulation changes RG proliferation. We sought to explore the effect of histone deacetylase (HDAC) activity on the proliferation of RGs in the visual optic tectum of Xenopus laevis. We found that the number of BrdU-labeled precursor cells along the ventricular layer of the tectum decrease developmentally from stage 46 to stage 49. The co-labeling of BrdU-positive cells with brain lipid-binding protein (BLBP), a radial glia marker, showed that the majority of BrdU-labeled cells along the tectal midline are RGs. BLBP-positive cells are also developmentally decreased with the maturation of the brain. Furthermore, HDAC1 expression is developmentally down-regulated in tectal cells, especially in the ventricular layer of the tectum. Pharmacological blockade of HDACs using Trichostatin A (TSA) or Valproic acid (VPA) decreased the number of BrdU-positive, BLBP-positive and co-labeling cells. Specific knockdown of HDAC1 by a morpholino (HDAC1-MO) decreased the number of BrdU- and BLBP-labeled cells and increased the acetylation level of histone H4 at lysine 12 (H4K12). The visual deprivation-induced increase in BrdU- and BLBP-positive cells was blocked by HDAC1 knockdown at stage 49 tadpoles. These data demonstrate that HDAC1 regulates radial glia cell proliferation in the developing optical tectum of Xenopus laevis.

Highlights

  • The maturation of the central nervous system (CNS) is mainly determined by the proliferation and differentiation of progenitor cells, which are key processes related to our understanding of cell generation with respect to brain development and repair

  • To label the Radial glial cells (RGs) in the optic tectum at stage 46 in vivo, the midbrain ventricle of the Xenopus tectum was injected with a construct that expressed enhanced green fluorescent protein (eGFP) under a CMV promoter (CMV::eGFP), and one side of the tectum was transfected by unilateral brain electroporation (Fig. 1A)

  • The majority of fluorescently labeled RGs were labeled with brain lipid-binding protein (BLBP), indicating that we can use BLBP immunostaining as a marker for the detections of RGs as shown before [25]

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Summary

Introduction

The maturation of the central nervous system (CNS) is mainly determined by the proliferation and differentiation of progenitor cells, which are key processes related to our understanding of cell generation with respect to brain development and repair. How progenitor cells are generated and differentiate into neurons that integrate into functional neural circuits in vivo is still relatively unknown. Radial glial cells (RGs), which originate from the neural epithelium, have. HDAC1 in Radial Glia Proliferation for Hangzhou “131” Talents to WS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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