Characterization of leukemia-associated Rho guanine nucleotide exchange factor (LARG) expression during murine development

Cell Tissue Res. 2003 Dec;314(3):361-6. doi: 10.1007/s00441-003-0802-5. Epub 2003 Sep 26.


LARG (leukemia-associated Rho guanine nucleotide exchange factor, ARHGEF12) was originally identified as a fusion partner of the MLL gene at 11q23 in human acute myeloid leukemia. We have previously demonstrated that the LARG protein activates RhoA, a member of the Rho family of small GTPases, by catalyzing the exchange of GTP for GDP. Experiments in Drosophila melanogaster have implicated RhoA and its regulators in a spectrum of developmental processes-including gastrulation, neurite outgrowth, and epidermal morphogenesis; however, the role of these genes during mammalian development is incompletely understood. Herein, we investigate the expression of the murine LARG homologue during embryogenesis and in adult animals, by a combination of mRNA in situ hybridization and immunohistochemical detection of the LARG protein. We observe that LARG transcript and protein are undetectable prior to embryonic day 14. Beginning at this stage, LARG is expressed in the skin, intestinal epithelium, and smooth muscle layers of the intestine, bronchi, and vasculature. This specific distribution is maintained at later stages of development and into adulthood. Finally, we demonstrate colocalization of the LARG protein with the insulin-like growth factor-I (IGF-1) receptor, suggesting a potential physiologic role for LARG as an activator of RhoA in response to IGF-1.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Vessels / cytology
  • Blood Vessels / embryology
  • Blood Vessels / metabolism
  • Bronchi / cytology
  • Bronchi / embryology
  • Bronchi / metabolism
  • Cell Differentiation / genetics
  • Female
  • Fetus
  • Gene Expression Regulation, Developmental / genetics
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Insulin-Like Growth Factor I / metabolism
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / embryology
  • Intestinal Mucosa / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth / cytology
  • Muscle, Smooth / embryology
  • Muscle, Smooth / metabolism
  • Organ Specificity
  • RNA, Messenger / metabolism
  • Receptor, IGF Type 1 / metabolism*
  • Rho Guanine Nucleotide Exchange Factors
  • Skin / cytology
  • Skin / embryology
  • Skin / metabolism
  • rho GTP-Binding Proteins / metabolism*


  • Arhgef12 protein, mouse
  • Guanine Nucleotide Exchange Factors
  • RNA, Messenger
  • Rho Guanine Nucleotide Exchange Factors
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • rho GTP-Binding Proteins