HDAC1 Regulates the Proliferation of Radial Glial Cells in the Developing Xenopus Tectum

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.

Pattern of Neurogenesis and Identification of Neuronal Progenitor Subtypes during Pallial Development in Xenopus laevis

“…Comparatively, the current results in the telencephalon of Xenopus with previous studies in other brain regions, such as the optic tectum, the number of dividing precursor cells along the tectal ventricular layer decreased through development from stage 46 to stage 49 (Tao et al, 2015), which is largely similar to the observations in the pallium, specially in the pallium versus SPa. These results concur with similar data reported in the spinal cord (Thuret et al, 2015).…”

“…Although general patterns of cell proliferation in the anuran brain have been studied (Wullimann et al, 2005; Chapman et al, 2006; Raucci et al, 2006; Simmons et al, 2006; Coen et al, 2007; Denver et al, 2009; Tao et al, 2015; Thuret et al, 2015), no detailed analysis of the pallium has been performed. We have selected some markers of the main proliferative events described in other vertebrates (PH3, PCNA and BrdU assays), which had previously been successfully used in Xenopus (D’Amico et al, 2011, 2013; Auger et al, 2012; McKeown et al, 2013) and allowed us to conduct birth-dating and mitotic rate analysis.…”

An Evolutionarily Conserved SoxB-Hdac2 Crosstalk Regulates Neurogenesis in a Cnidarian

“…Class I histone deacetylases (HDACs) – in particular, the homologous enzymes Hdac1 and Hdac2 – are emerging players in nervous system development and function (Castelo-Branco et al, 2014; Hagelkruys et al, 2014; Montgomery et al, 2009; Tao et al, 2015; Wang et al, 2010; Ye et al, 2009). The significance of HDACs became evident in recent studies showing that both histone acetylation and deacetylation act during neurogenesis in a highly context-dependent manner (MacDonald and Roskams, 2008; Montgomery et al, 2009; Yao and Jin, 2014).…”

Visual experience dependent regulation of neuronal structure and function by histone deacetylase 1 in developing Xenopus tectum in vivo

“…The HDAC1 orthologues in homo sapiens and Xenopus laevis share 90.46% protein sequence homology (Tao et al, ). We found that HDAC1 was ubiquitously expressed throughout the cell layer and predominantly localized within the cell nuclei of the Xenopus tectum at stage 47 [Fig.…”

“…In contrast, acute overexpression of HDAC1 regulates extinction of fear memory in the adult brain (Bahari‐Javan et al, ) and inhibitory synaptic transmission in cultured hippocampal slices (Hanson et al, ). Although HDAC1 has been shown to play a role in neural proliferation/differentiation (Yamaguchi et al, ; Cunliffe and Casaccia‐Bonnefil, ; Brunmeir et al, ; Ye et al, ; Dovey et al, ; Conway et al, ; Jacob et al, ; Tao et al, ), learning and memory (Bahari‐Javan et al, ), neuronal survival and death (Kim et al, ; Kim et al, ; Bardai et al, ) and neurological diseases (Abel and Zukin, ; Chen et al, ; Jia et al, ; Rudenko and Tsai, ), there is limited evidence for HDAC1 in neuronal dendritic growth and structural plasticity. Recent work has shown that visual avoidance behavior can be used to measure the function of the visual circuit (Dong et al, ; Shen et al, ); however, the role of HDAC1 in the behavior and underlying cellular mechanisms remain unclear.…”