PRMT5 is essential for the maintenance of chondrogenic progenitor cells in the limb bud.
During embryonic development, undifferentiated progenitor cells balance the generation of additional progenitor cells with differentiation. Within the developing limb, cartilage cells differentiate from mesodermal progenitors in an ordered process that results in the specification of the correct number of appropriately sized skeletal elements. The internal pathways by which these cells maintain an undifferentiated state while preserving their capacity to differentiate is unknown. Here, we report that the arginine methyltransferase PRMT5 has a crucial role in maintaining progenitor cells. Mouse embryonic buds lacking PRMT5 have severely truncated bones with wispy digits lacking joints. This novel phenotype is caused by widespread cell death that includes mesodermal progenitor cells that have begun to precociously differentiate into cartilage cells. We propose that PRMT5 maintains progenitor cells through its regulation of Bmp4 Intriguingly, adult and embryonic stem cells also require PRMT5 for maintaining pluripotency, suggesting that similar mechanisms might regulate lineage-restricted progenitor cells during organogenesis.
Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA.
Jacqueline L
JL
Norrie
Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA.
Qiang
Q
Li
Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA.
Swanie
S
Co
Cancer and Developmental Biology Laboratory, CCR, NCI, Frederick, MD 21702, USA.
Bau-Lin
BL
Huang
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E3638, Baltimore, MD 21205, USA.
Ding
D
Ding
Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA.
Jann C
JC
Uy
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E3638, Baltimore, MD 21205, USA.
Zhicheng
Z
Ji
Cancer and Developmental Biology Laboratory, CCR, NCI, Frederick, MD 21702, USA.
Susan
S
Mackem
Department of Epigenetics & Molecular Carcinogenesis, M.D. Anderson Cancer Center, 1808 Park Road 1C (P.O. Box 389), Smithville, TX 78957, USA.
Mark T
MT
Bedford
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Antonella
A
Galli
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room E3638, Baltimore, MD 21205, USA.
Hongkai
H
Ji
Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway Stop A4800, Austin, TX 78712, USA svokes@austin.utexas.edu.
Steven A
0000-0002-1724-0102
SA
Vokes
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002356:Cartilage / Q000166:cytology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005552:Forelimb / Q000002:abnormalities / Q000196:embryology*; D018878:Limb Buds / Q000196:embryology*; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C498518:Prmt5 protein, mouse; D011484:Protein-Arginine N-Methyltransferases
BMP4; Chondrogenesis; Limb development; PRMT5; Progenitor cells; SOX9