cAMP, an Activator of Protein Kinase A, Suppresses the Expression of Sonic Hedgehog

Noveen, Alexander; Jiang, Ting‐Xin; Chuong, Cheng‐Ming

doi:10.1006/bbrc.1996.0202

Cited by 30 publications

(12 citation statements)

References 19 publications

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“…The gene expression pattern of Gbx1 in the epidermis of feather bud was almost the same as that of the HB9 homeobox gene, as we reported previously (Kosaka et al, 2000b). Other than homeobox genes, the genes encoding morphogenetic proteins such as fibroblast growth factor (FGF; Widelitz et al, 1996), bone morphogenetic proteins (BMPs; Noramly and Morgan, 1998), sonic hedgehog (Shh; Bitgood and McMahon, 1995;Noveen et al, 1996;Ting-Berreth and Chuong, 1996), Wnt 7a (Widelitz et al, 1999), Notch, Delta, Serrate (Chen et al, 1997), and b-catenin (Noramly et al, 1999) are involved in the early stage of feather development (Lin et al, 2006). The present study indicated that the expression pattern of Gbx1 mRNA was not consistent with the patterns of these signals.…”

Section: Discussionsupporting

confidence: 73%

Effects of retinoic acid and Gbx1 on feather‐bud formation and epidermal transdifferentiation in chick embryonic cultured dorsal skin

Obinata

Akimoto

2012

Developmental Dynamics

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Background: Retinoic acid, an active metabolite of retinol, is known to regulate cell proliferation, differentiation, and morphogenesis during normal development of many tissues. Using chick embryonic tarsometatarsal skin, we showed previously that the expression of Gbx1, a divergent homeobox gene, is increased in the epidermis through interaction with retinol-pretreated dermal fibroblasts followed by epidermal transdifferentiation to mucous epithelium. This present study was performed to elucidate the effects of retinoic acid and Gbx1 on feather-bud formation and epidermal transdifferentiation. Results: We showed that Gbx1 was expressed in the chick embryonic dorsal epidermis as early as at placode stage (Hamburger and Hamilton stage 31) and increased in amount during feather-bud formation. Treatment with 1 mM retinoic acid for 24 hr inhibited feather-bud formation and induced the transdifferentiation of the epidermis to a mucosal epithelium with a concomitant increase in Gbx1 mRNA expression in the epithelium. Furthermore, transient transfection of the epidermis with Gbx1 cDNA by electroporation induced elongation of the feather bud, but did not result in transdifferentiation. Conclusions: These results indicate that Gbx1 was involved in the feather-bud formation and was one of target genes of retinoic acid and that other signals in addition to Gbx1 were required for epidermal mucous transdifferentiation. Developmental Dynamics 241:1405-1412, 2012. V C 2012 Wiley Periodicals, Inc.Key words: Gbx1; homeobox gene; retinoic acid; skin; mucosal epithelium; transdifferentiation; feather-bud formation; chick embryo Key Findings:Gbx1 is involved in feather-bud formation. Retinoic acid inhibits feather-bud formation, induces transdifferentiation of epidermis to mucosal epithelium, and increases Gbx1 expression. Transfection of the epidermis with Gbx1 cDNA induces elongation of the feather bud, but does not induce transdifferentiation. Accepted 3 July 2012 Developmental DynamicsABBREVIATIONS aa amino acid DAPI 4 0 , 6-diamidino-2-phenylindole DIG digoxigenin MV microvilli PAS periodic acid-Schiff PBS phosphate-buffered saline.

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Section: Discussionsupporting

confidence: 73%

Effects of retinoic acid and Gbx1 on feather‐bud formation and epidermal transdifferentiation in chick embryonic cultured dorsal skin

Obinata

Akimoto

2012

Developmental Dynamics

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“…The gene expression pattern of Gbx1 in the epidermis of feather buds is almost the same as that of the HB9 homeobox gene, as we reported previously [42]. Other than homeobox genes, the genes encoding morphogenetic proteins such as fibroblast growth factors (FGFs) [49], bone morphogenetic proteins (BMPs) [50], sonic hedgehog (Shh) [51][52][53], Wnt 7a [54], Notch, Delta, Serrate [55], and β-catenin [56] are involved in the early stage of feather development [20]. Especially, FGF-, BMP-, Shh, and Wnt-signaling pathways play important roles in the morphogenesis of feather [20,49,50,53,54].…”

Section: Effects Of Ra On the Expression Of Homeobox Genes In Chick Esupporting

confidence: 56%

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

Akimoto

Miyaji

Morimoto-Kamata

et al. 2014

JDB

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Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470-488). However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA) for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal OPEN ACCESS J. Dev. Biol. 2014, 2 159 epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA) play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

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“…However, patterning by the hedgehog signaling pathway in flies and mice involves antagonizing the PKA pathway (19,60). Our results suggest that PKA may also impinge on patterning mediated by the HOX family.…”

Section: Discussionmentioning

confidence: 73%

Cell Signaling Switches HOX-PBX Complexes from Repressors to Activators of Transcription Mediated by Histone Deacetylases and Histone Acetyltransferases

Saleh

Rambaldi

Yang

et al. 2000

Molecular and Cellular Biology

187

180

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HOX proteins are sequence-specific DNA-binding transcription factors that play a crucial role in the specification of anteroposterior identity in the animal embryo (20, 54). Conservation within the DNA-binding homeodomains results in different HOX proteins recognizing similar regulatory elements with only modest preferences (reviewed in reference 27). High-affinity DNA binding is achieved when HOX proteins are heterodimerized with partners of the PBC family (mammalian PBX, Drosophila Extradenticle [EXD], and Caenorhabditis elegans CEH-20) (55). Mammalian MEIS1 has been shown to independently dimerize with HOX proteins and with PBX (11,57,78). Recently, trimeric complexes encompassing all three homeoproteins, HOX-PBX-MEIS, have also been characterized (77, 79). The MEIS-related protein PREP1, also known as PKNOX1, can additionally form a dimer with PBX, as well as a trimeric complex with HOX and PBX partners (6,7,15,34). While the majority of HOX monomers recognize a DNA core motif of TAAT (23), HOX-PBX, HOX-MEIS, and PBX-MEIS heterodimers recognize larger motifs resulting in a higher affinity and specificity of DNA binding by these homeoproteins (49).A conserved motif with the consensus YPWM is found N terminal to the homeodomain of HOX proteins from paralogous groups 1 to 8. The YPWM motif contacts the PBX homeodomain and is strictly required for cooperative DNA binding by PBX and HOX partners (49,50). A conserved W in HOX proteins from groups 9 and 10 performs a similar function (12).The downstream targets of mammalian HOX proteins have been poorly characterized. The best-characterized targets are some Hox genes known to be positively autoregulated by their own products or cross-regulated by the products of other Hox genes (26,68,69). In these instances, HOX-PBX complexes act as activators of transcription. For example, the Hoxb1 autoregulatory element (ARE) contains three binding sites for HOX-PBX complexes. These sites are required to direct expression of a Hoxb1 transgene in rhombomere 4 (r4) of the developing hindbrain (68).Genetic and molecular studies have provided evidence supporting a negative regulatory role for HOX proteins (43). In the case of decapentaplegic (dpp) regulation in Drosophila, repression by HOX proteins dominates over activation (9). This implies active transcriptional repression by HOX proteins (9,25,46). In addition, in vitro mapping studies have characterized repression domains in different HOX proteins, as well as in the PBX partner (13,45,75). Therefore, HOX proteins may be activators or repressors in a context-dependent manner.By analogy to nuclear receptors, HOX-PBX complexes are likely to achieve transcriptional repression or activation through differential association with coactivators and corepressors (81). One class of coregulators are the histone acetyltransferases (HATs) and the histone deacetylases (HDACs), which modify chromatin as well as nonhistone proteins. The HATs include GCN5, PCAF, CREB-binding protein (CBP)/p300, the steroid receptor coactivator class, and the MY...

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cAMP, an Activator of Protein Kinase A, Suppresses the Expression of Sonic Hedgehog

Cited by 30 publications

References 19 publications

Effects of retinoic acid and Gbx1 on feather‐bud formation and epidermal transdifferentiation in chick embryonic cultured dorsal skin

Effects of retinoic acid and Gbx1 on feather‐bud formation and epidermal transdifferentiation in chick embryonic cultured dorsal skin

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

Cell Signaling Switches HOX-PBX Complexes from Repressors to Activators of Transcription Mediated by Histone Deacetylases and Histone Acetyltransferases

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