title: Protein kinase A and protein kinase C modulators have reciprocal effects on mesenchymal condensation during skin appendage morphogenesis.
abstract: The molecular signaling of secondary induction is a fundamental process in organogenesis during embryonic development. To study the signal transduction pathways involved, we used developing chicken skin as a model and focused on the roles of intracellular signaling during feather morphogenesis. Protein kinase C (PKC) immunoreactivity increases in the whole layer of forming dermis around H and H stage 30. This is followed by a gradual and highly localized decrease of PKC expression immediately beneath each forming feather germ. In contrast, cAMP response element binding protein (CREB) is ubiquitously expressed in both epithelium and mesenchyme. From stage 29 on, phosphorylated CREB (P-CREB), reflecting the activity of protein kinase A (PKA), begins to be seen in placode but not in interplacode epithelia. P-CREB is also expressed in bud mesenchyme transiently between stages 33 and 36, but not in the interbud mesenchyme. The presence and activity of PKC, PKA, and P-CREB in developing chicken skin are further characterized by immunoblot, kinase activity, and gel shift assays. To explore their physiological significance, embryonic chicken dorsal skin explants were treated with different modulators in medium or in beads for localized effects. The results showed that PKA activators and PKC inhibitors can expand a feather bud domain by enhancing dermal condensation, while PKC activators and PKA inhibitors can expand interbud domains. Neural cell adhesion molecule (N-CAM) is involved in dermal condensation. We observed that activation of PKA causes diffused expression of N-CAM in mesenchyme while activation of PKC causes the disappearance of N-CAM in precondensed mesenchymal regions. A model of how the well-concerted PKA and PKC signaling may be involved in the formation and size regulation of dermal condensation is presented.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles 90033, USA.
authors.forename: A
authors.initials: A
authors.lastname: Noveen
authors.forename: T X
authors.initials: TX
authors.lastname: Jiang
authors.forename: C M
authors.initials: CM
authors.lastname: Chuong
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology; D002642:Chick Embryo; D017362:Cyclic AMP Response Element-Binding Protein / Q000032:analysis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000502:physiology*; D005241:Feathers / Q000196:embryology*; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000502:physiology*; D009024:Morphogenesis; D011493:Protein Kinase C / Q000032:analysis / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D017362:Cyclic AMP Response Element-Binding Protein; D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C