Leading science, pioneering therapies
CRM Publications

The methyl-CpG binding proteins Mecp2, Mbd2 and Kaiso are dispensable for mouse embryogenesis, but play a redundant function in neural differentiation.

TitleThe methyl-CpG binding proteins Mecp2, Mbd2 and Kaiso are dispensable for mouse embryogenesis, but play a redundant function in neural differentiation.
Publication TypeJournal Article
Year of Publication2009
AuthorsCaballero IM, Hansen J, Leaford D, Pollard SM, Hendrich B
JournalPLoS One
Volume4
Issue1
Paginatione4315
Date Published2009
ISSN1932-6203
KeywordsAnimals, Animals, Newborn, Cell Differentiation, Cell Line, DNA-Binding Proteins, Embryonic Development, Methyl-CpG-Binding Protein 2, Mice, Mice, Knockout, Neurons, Stem Cells, Transcription Factors
Abstract

BACKGROUND: The precise molecular changes that occur when a neural stem (NS) cell switches from a programme of self-renewal to commit towards a specific lineage are not currently well understood. However it is clear that control of gene expression plays an important role in this process. DNA methylation, a mark of transcriptionally silent chromatin, has similarly been shown to play important roles in neural cell fate commitment in vivo. While DNA methylation is known to play important roles in neural specification during embryonic development, no such role has been shown for any of the methyl-CpG binding proteins (Mecps) in mice.

METHODOLOGY/PRINCIPAL FINDINGS: To explore the role of DNA methylation in neural cell fate decisions, we have investigated the function of Mecps in mouse development and in neural stem cell derivation, maintenance, and differentiation. In order to test whether the absence of phenotype in singly-mutant animals could be due to functional redundancy between Mecps, we created mice and neural stem cells simultaneously lacking Mecp2, Mbd2 and Zbtb33. No evidence for functional redundancy between these genes in embryonic development or in the derivation or maintenance of neural stem cells in culture was detectable. However evidence for a defect in neuronal commitment of triple knockout NS cells was found.

CONCLUSIONS/SIGNIFICANCE: Although DNA methylation is indispensable for mammalian embryonic development, we show that simultaneous deficiency of three methyl-CpG binding proteins genes is compatible with apparently normal mouse embryogenesis. Nevertheless, we provide genetic evidence for redundancy of function between methyl-CpG binding proteins in postnatal mice.

DOI10.1371/journal.pone.0004315
Alternate JournalPLoS ONE
PubMed ID19177165
PubMed Central IDPMC2627903
Grant List081816 / / Wellcome Trust / United Kingdom
G0300723 / / Medical Research Council / United Kingdom
G0800784 / / Medical Research Council / United Kingdom
G19/38 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom