The tumor suppressor Pml regulates cell fate in the developing neocortex.
The control of cell fate in neural progenitor cells is critical for nervous system development. Nevertheless, the processes involved are only partially known. We found that the expression of the tumor suppressor Pml was restricted to neural progenitor cells (NPCs) in the developing neocortex of the mouse. Notably, in Pml(-/-) cortices, the overall number of proliferating NPCs was increased and transition between the two major progenitor types, radial glial cells and basal progenitors, was impaired. This in turn resulted in reduced differentiation and an overall decrease in the thickness of the cortex wall. In NPCs, Pml regulated the subcellular distribution of the retinoblastoma protein (pRb) and the protein phosphatase 1alpha, triggering pRb dephosphorylation. Together, these findings reveal an unexpected role of Pml in controlling the function of NPCs in the CNS.
Regad
Tarik
T
Medicial Research Council Toxicology Unit, University of Leicester, Box 138 Lancaster Road, Leicester LE1 7JL, UK.
Bellodi
Cristian
C
Nicotera
Pierluigi
P
Salomoni
Paolo
P
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D009929:Organ Size; D010766:Phosphorylation; D011247:Pregnancy; D000071156:Promyelocytic Leukemia Protein; D054645:Protein Phosphatase 1 / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D054645:Protein Phosphatase 1