title: High-level activation of cyclic AMP signaling attenuates bone morphogenetic protein 2-induced sympathoadrenal lineage development and promotes melanogenesis in neural crest cultures.
abstract: The intensity of cyclic AMP (cAMP) signaling is a differential instructive signal in neural crest (NC) cell specification. By an unknown mechanism, sympathoadrenal lineage specification is suppressed by high-level activation of cAMP signaling. In NC cultures, high-level activation of cAMP signaling mediates protein kinase A (PKA)-dependent Rap1-B-Raf-ERK1/2 activation, leading to cytoplasmic accumulation of phospho-Smad1, thus terminating bone morphogenetic protein 2 (BMP2)-induced sympathoadrenal cell development. Concurrently, cAMP signaling induces transcription of the melanocyte-determining transcription factor Mitf and melanogenesis. dnACREB and E1A inhibit Mitf expression and melanogenesis, supporting the notion that CREB activation is necessary for melanogenesis. However, constitutively active CREB(DIEDML) without PKA activation is insufficient for Mitf expression and melanogenesis, indicating PKA regulates additional aspects of Mitf transcription. Thus, high-level activation of cAMP signaling plays a dual role in NC cell differentiation: attenuation of BMP2-induced sympathoadrenal cell development and induction of melanogenesis. We conclude the intensity of activation of signal transduction cascades determines cell lineage segregation mechanisms.
authors.affiliation: Department of Basic Medical Sciences, 625 Harrison Street, Purdue University, West Lafayette, IN 47907-2026, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Ji
authors.forename: Ourania M
authors.initials: OM
authors.lastname: Andrisani
mesh_terms: D000311:Adrenal Glands / Q000166:cytology / Q000254:growth & development; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage; D002478:Cells, Cultured; D005576:Colforsin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D051739:Microphthalmia-Associated Transcription Factor; D009432:Neural Crest / Q000166:cytology*; D011784:Quail; D015290:Second Messenger Systems / Q000502:physiology*; D051785:Smad Proteins; D013564:Sympathetic Nervous System / Q000254:growth & development; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D051785:Smad Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D005576:Colforsin; D005346:Fibroblast Growth Factors; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases