Alterations in Ca2+-dependent and cAMP-dependent signaling pathways affect neurogenesis and melanogenesis of quail neural crest cells in vitro.
Trunk neural crest cells primarily form neurons, nerve supportive cells of the peripheral nervous system and melanocytes. We are interested in signal transduction pathways that affect the production of peripheral neurons or melanocytes. Quail neural crest cell cultures were treated with a variety of drugs that affect components of protein kinase A- (PKA-), protein kinase C- (PKC-) and inositol-3-phosphate- (I3P-) dependent pathways. Forskolin, a drug that increases cAMP levels, augmented melanocyte populations and reduced neuronal populations in our cultures. H8 and H89, two drugs that inhibit PKA, reduced melanocyte populations well below control levels. Down regulation of PKC with a phorbol ester, PMA, or with calphostin C inhibited neurogenesis. PMA also enhanced melanogenesis. Increasing intracellular calcium levels (with A23187 or thapsigargin) resulted in cultures with few melanocytes but many neurons, compared to untreated controls. An antagonist of the I3P pathway, wortmannin, prevented the appearance of neurons but did not affect melanocyte populations. In summary, molecules that altered the PKA-dependent pathway affected melanogenesis. Manipulations of the I3P and/or PKC-dependent pathways influenced neurogenesis. Stimulation of one pathway often inhibited appearance of cells associated with the alternative pathway.
Department of Biochemistry and Molecular Biology, University of Texas-M.D. Anderson Cancer Center, Houston, TX, USA.
Yvonne A
YA
Evrard
Ladan
L
Mohammad-Zadeh
Beatrice
B
Holton
D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D009432:Neural Crest / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000032:analysis; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011784:Quail / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction
D016900:Neurofilament Proteins; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C