MRG15, a component of HAT and HDAC complexes, is essential for proliferation and differentiation of neural precursor cells

• Published in: Journal of neuroscience research Vol. 87; no. 7; pp. 1522 - 1531
• Main Authors: Chen, Meizhen, Takano-Maruyama, Masumi, Pereira-Smith, Olivia M., Gaufo, Gary O., Tominaga, Kaoru
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.05.2009
• Subjects: Adenoviridae; Animals; Apoptosis - physiology; Brain - embryology; Brain - physiology; Bromodeoxyuridine; Cell Proliferation; Cells, Cultured; chromatin; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; development; epigenetics; gene expression; Genetic Vectors; Glial Fibrillary Acidic Protein; Immunohistochemistry; In Situ Nick-End Labeling; Intermediate Filament Proteins - metabolism; Mice; Mice, Knockout; Nerve Tissue Proteins - metabolism; Nestin; neural precursor cell; Neurogenesis - physiology; Neurons - cytology; Neurons - physiology; Stem Cells - cytology; Stem Cells - physiology; Trans-Activators - genetics; Trans-Activators - metabolism; Tubulin - metabolism
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.21976

Neurogenesis during development depends on the coordinated regulation of self‐renewal and differentiation of neural precursor cells (NPCs). Chromatin regulation is a key step in self‐renewal activity and fate decision of NPCs. However, the molecular mechanism or mechanisms of this regulation is not fully understood. Here, we demonstrate for the first time that MRG15, a chromatin regulator, is important for proliferation and neural fate decision of NPCs. Neuroepithelia from Mrg15‐deficient embryonic brain are much thinner than those from control, and apoptotic cells increase in this region. We isolated NPCs from Mrg15‐deficient and wild‐type embryonic whole brains and produced neurospheres to measure the self‐renewal and differentiation abilities of these cells in vitro. Neurospheres culture from Mrg15‐deficient embryo grew less efficiently than those from wild type. Measurement of proliferation by means of BrdU (bromodeoxyuridine) incorporation revealed that Mrg15‐deficient NPCs have reduced proliferation ability and apoptotic cells do not increase during in vitro culture. The reduced proliferation of Mrg15‐deficient NPCs most likely accounts for the thinner neuroepithelia in Mrg15‐deficient embryonic brain. Moreover, we also demonstrate Mrg15‐deficient NPCs are defective in differentiation into neurons in vitro. Our results demonstrate that MRG15 has more than one function in neurogenesis and defines a novel role for this chromatin regulator that integrates proliferation and cell‐fate determination in neurogenesis during development. © 2008 Wiley‐Liss, Inc.