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Retinoic acid induces CDK inhibitors and growth arrest specific ( Gas ) genes in neural crest cells
Author(s) -
Wang Linping,
Mear John P.,
Kuan ChiaYi,
Colbert Melissa C.
Publication year - 2005
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/j.1440-169x.2005.00788.x
Subject(s) - retinoic acid , neural crest , microbiology and biotechnology , gene , crest , chemistry , biology , biochemistry , physics , quantum mechanics
Retinoic acid (RA), the active metabolite of vitamin A, regulates cellular growth and differentiation during embryonic development. In excess, this vitamin is also highly teratogenic to animals and humans. The neural crest is particularly sensitive to RA, and high levels adversely affect migration, proliferation and cell death. We investigated potential gene targets of RA associated with neural crest proliferation by determining RA‐mediated changes in gene expression over time, using microarrays. Statistical analysis of the top ranked RA‐regulated genes identified modest changes in multiple genes previously associated with cell cycle control and proliferation including the cyclin‐dependent kinase inhibitors Cdkn1a (p21), Cdkn2b (p15 INK4b ), and Gas3/PMP22 . The expression of p21 and p15 INK4b contribute to decreased proliferation by blocking cell cycle progression at G1‐S. This checkpoint is pivotal to decisions regulating proliferation, apoptosis, or differentiation. We have also confirmed the overexpression of Gas3/PMP22 in RA‐treated neural crests, which is associated with cytoskeletal changes and increased apoptosis. Our results suggest that increases in multiple components of diverse regulatory pathways have an overall cumulative effect on cellular decisions. This heterogeneity contributes to the pleiotropic effects of RA, specifically those affecting proliferation and cell death.