Essential roles of mgcRacGAP in multilineage differentiation and survival of murine hematopoietic cells.
MgcRacGAP, a negative regulator for Rho family GTPases, has been shown to play important roles in cytokinesis using several cell lines. However, the physiological role of mgcRacGAP in multilineage hematopoietic development remains unclear. Here, we conditionally ablated mgcRacGAP in vivo to clarify this issue. As the result, we found that normal hematopoietic development including proliferation and survival requires mgcRacGAP. We also found that depletion of mgcRacGAP in hematopoietic cells results in a marked decrease in c-Kit(+)Sca-1(+)Lin(-) cells, suggesting that mgcRacGAP is required for the maintenance of the hematopoietic stem cells. In addition, B cells in which mgcRacGAP had been selectively ablated showed proliferation failure and fell into apoptosis. Taken together, mgcRacGAP is now shown to play a indispensable role in the development of hematopoietic cells in vivo.
Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Suehiro-cho 1-7-22, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Takayuki
T
Yamada
Tomohiro
T
Kurosaki
Masaki
M
Hikida
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051020:bcl-X Protein / Q000378:metabolism
C494812:Bcl2l1 protein, mouse; D020690:GTPase-Activating Proteins; D051020:bcl-X Protein; C115995:mgcRacGAP