Biologie unicellulaire

Abstrait

Rest as a New Transcription Factor to Control Neural Crest Development

Hitomi Aoki and Takahiro Kunisada

RE1-silencing transcription factor (Rest), also known as NRSF (neuro-restrictive silencer factor), is a negative regulator of neuron-specific genes and expressed during embryonic development to prevent neural gene expression in non-neuronal cells. However, Rest null mice die by E11.5, prior to which the growth retardation caused by widespread apoptotic cell death has precluded further analyses of the potential role of Rest in vivo. In order to investigate the function of Rest in neural crest cells (NCCs) which are known to differentiate into neuronal and nonneuronal lineages, we established NCC-specific homozygous Rest conditional knockout (CKO) mice and observed their neonatal death caused by the defect of enteric nerve cells derived from NCCs. The viable heterozygous NCCspecific Rest CKO mice showed the white spotting phenotype, associated with a reduction in the number of melanoblasts, a non-neuronal derivative of NCCs, in embryonic skin. These results suggest the expression of REST during the early NCC specification stage is necessary for the proper development of NCCs. To fully understand the mechanisms of white spot formation and postnatal death or embryonic lethality mediated by the Rest ablation, future experiments should focus on single cell analysis to characterize the detailed cellular events such as reduced cell cycle, apoptosis, change of the cell fate to well explain the observed phenotypic changes.