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PI 3K/Akt pathway regulates retinoic acid‐induced Hox gene expression in F9 cells
Author(s) -
Lee Youra,
Lee JiYeon,
Kim Myoung Hee
Publication year - 2014
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12152
Subject(s) - retinoic acid , pi , hox gene , retinoic acid inducible orphan g protein coupled receptor , microbiology and biotechnology , gene , chemistry , protein kinase b , gene expression , biology , signal transduction , retinoic acid receptor , genetics , biochemistry
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 PI 3K/Akt pathway was also reported to play an essential role in the process of RA ‐induced cell differentiation. Therefore, we tested whether the PI 3K/Akt pathway is involved in RA ‐induced Hox gene expression in a F9 murine embryonic teratocarcinoma cells. To examine the effect of PI 3K/Akt signaling on RA ‐induced initiation of collinear expression of Hox genes, F9 cells were treated with RA in the presence or absence of PI 3K inhibitor LY 294002, 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 LY 294002 was applied along with RA , collinear expression induced by RA was delayed, suggesting that the PI 3K/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 LY 294002 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.