MRG15, a component of HAT and HDAC complexes, is essential for proliferation and differentiation of neural precursor cells.
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.
Chen
Meizhen
M
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245, USA.
Takano-Maruyama
Masumi
M
Pereira-Smith
Olivia M
OM
Gaufo
Gary O
GO
Tominaga
Kaoru
K
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000196:embryology / Q000502:physiology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors; D005904:Glial Fibrillary Acidic Protein; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C471162:MRG15 protein, mouse; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D015534:Trans-Activators; D014404:Tubulin; D001973:Bromodeoxyuridine