title: PI3K/Akt pathway regulates retinoic acid-induced Hox gene expression in F9 cells.
abstract: Retinoic acid (RA), the most potent natural form of vitamin A, is a key morphogen in vertebrate development and a potent regulator of both adult and embryonic cell differentiation. Specifically, RA regulates clustered Hox gene expression during embryogenesis and is required to establish the anteroposterior body plan. The PI3K/Akt pathway was also reported to play an essential role in the process of RA-induced cell differentiation. Therefore, we tested whether the PI3K/Akt pathway is involved in RA-induced Hox gene expression in a F9 murine embryonic teratocarcinoma cells. To examine the effect of PI3K/Akt signaling on RA-induced initiation of collinear expression of Hox genes, F9 cells were treated with RA in the presence or absence of PI3K inhibitor LY294002, and time-course gene expression profiles for all 39 Hox genes located in four different clusters-Hoxa, Hoxb, Hoxc, and Hoxd-were analyzed. Collinear expression of Hoxa and -b cluster genes was initiated earlier than that of the -c and -d clusters upon RA treatment. When LY294002 was applied along with RA, collinear expression induced by RA was delayed, suggesting that the PI3K/Akt signaling pathway somehow regulates RA-induced collinear expression of Hox genes in F9 cells. The initiation of Hox collinear expression by RA and the delayed expression following LY294002 in F9 cells would provide a good model system to decipher the yet to be answered de novo collinear expression of Hox genes during gastrulation, which make the gastrulating cells to remember their positional address along the AP body axis in the developing embryo.
authors.affiliation: Embryology Laboratory, Department of Anatomy, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul, 120-752, Korea.
authors.forename: Youra
authors.initials: Y
authors.lastname: Lee
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002867:Chromones / Q000494:pharmacology; D054278:Embryonal Carcinoma Stem Cells / Q000378:metabolism*; D054262:Gastrulation / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects* / Q000502:physiology; D005801:Genes, Homeobox / Q000502:physiology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D059467:Transcriptome; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002867:Chromones; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D014212:Tretinoin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: PI3K/Akt signal; Retinoic acid; anteroposterior axis; collinear expression of Hox genes; development