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Article: Retinoic acid signaling and the initiation of mammary gland development

TitleRetinoic acid signaling and the initiation of mammary gland development
Authors
KeywordsMammary Gland Development
Rar-Β
Retinoic Acid
Tbx3
Wnt10b
Issue Date2012
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbio
Citation
Developmental Biology, 2012, v. 365 n. 1, p. 259-266 How to Cite?
AbstractRetinoic acid receptors (RARs), which are involved in retinoic acid signal transduction, are essential for maintaining the differentiated state of epithelial tissues. Mammary glands are skin appendages whose development is initiated through continuous cell-cell interactions between the ectoderm and the adjacent mesenchyme. Considerable progress has been made in elucidating the molecular basis of these interactions in mammary gland formation in mouse embryos, including the network of initiating signals comprising Fgfs, Wnts and Bmps involved in gland positioning and the transcription factors, Tbx3 and Lef1, essential for mammary gland development. Here, we provide evidence that retinoic acid signaling may also be involved in mammary gland development. We documented the expression of gene-encoding enzymes that produce retinoic acid (Raldh2) and enzymes that degrade it (Cyp26a1, Cyp26b1). We also analyzed the expression of RAR-β, a direct transcriptional target of retinoic acid signaling. Raldh2 and RAR-β were expressed in E10-E10.5 mouse embryos in somites adjacent to the flank region where mammary buds 2, 3 and 4 develop. These expression patterns overlapped with that of Fgf10, which is known to be required for mammary gland formation. RAR-β was also expressed in the mammary mesenchyme in E12 mouse embryos; RAR-β protein was expressed in the mammary epithelium and developing fat pad. Retinoic acid levels in organ cultures of E10.5 mouse embryo flanks were manipulated by adding either retinoic acid or citral, a retinoic acid synthesis inhibitor. Reduced retinoic acid synthesis altered the expression of genes involved in retinoic acid homeostasis and also demonstrated that retinoic acid signaling is required for Tbx3 expression, whereas high levels of retinoic acid signaling inhibited Bmp4 expression and repressed Wnt signaling. The results of the experiments using RNAi against Tbx3 and Wnt10b suggested feedback interactions that regulate retinoic acid homeostasis in mammary gland-forming regions. We produced a molecular model for mammary gland initiation that incorporated retinoic acid signaling. © 2012 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/169592
ISSN
2015 Impact Factor: 3.155
2015 SCImago Journal Rankings: 2.554
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCho, KWen_US
dc.contributor.authorKwon, HJen_US
dc.contributor.authorShin, JOen_US
dc.contributor.authorLee, JMen_US
dc.contributor.authorCho, SWen_US
dc.contributor.authorTickle, Cen_US
dc.contributor.authorJung, HSen_US
dc.date.accessioned2012-10-25T04:53:14Z-
dc.date.available2012-10-25T04:53:14Z-
dc.date.issued2012en_US
dc.identifier.citationDevelopmental Biology, 2012, v. 365 n. 1, p. 259-266en_US
dc.identifier.issn0012-1606en_US
dc.identifier.urihttp://hdl.handle.net/10722/169592-
dc.description.abstractRetinoic acid receptors (RARs), which are involved in retinoic acid signal transduction, are essential for maintaining the differentiated state of epithelial tissues. Mammary glands are skin appendages whose development is initiated through continuous cell-cell interactions between the ectoderm and the adjacent mesenchyme. Considerable progress has been made in elucidating the molecular basis of these interactions in mammary gland formation in mouse embryos, including the network of initiating signals comprising Fgfs, Wnts and Bmps involved in gland positioning and the transcription factors, Tbx3 and Lef1, essential for mammary gland development. Here, we provide evidence that retinoic acid signaling may also be involved in mammary gland development. We documented the expression of gene-encoding enzymes that produce retinoic acid (Raldh2) and enzymes that degrade it (Cyp26a1, Cyp26b1). We also analyzed the expression of RAR-β, a direct transcriptional target of retinoic acid signaling. Raldh2 and RAR-β were expressed in E10-E10.5 mouse embryos in somites adjacent to the flank region where mammary buds 2, 3 and 4 develop. These expression patterns overlapped with that of Fgf10, which is known to be required for mammary gland formation. RAR-β was also expressed in the mammary mesenchyme in E12 mouse embryos; RAR-β protein was expressed in the mammary epithelium and developing fat pad. Retinoic acid levels in organ cultures of E10.5 mouse embryo flanks were manipulated by adding either retinoic acid or citral, a retinoic acid synthesis inhibitor. Reduced retinoic acid synthesis altered the expression of genes involved in retinoic acid homeostasis and also demonstrated that retinoic acid signaling is required for Tbx3 expression, whereas high levels of retinoic acid signaling inhibited Bmp4 expression and repressed Wnt signaling. The results of the experiments using RNAi against Tbx3 and Wnt10b suggested feedback interactions that regulate retinoic acid homeostasis in mammary gland-forming regions. We produced a molecular model for mammary gland initiation that incorporated retinoic acid signaling. © 2012 Elsevier Inc.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ydbioen_US
dc.relation.ispartofDevelopmental Biologyen_US
dc.subjectMammary Gland Developmenten_US
dc.subjectRar-Βen_US
dc.subjectRetinoic Aciden_US
dc.subjectTbx3en_US
dc.subjectWnt10ben_US
dc.titleRetinoic acid signaling and the initiation of mammary gland developmenten_US
dc.typeArticleen_US
dc.identifier.emailJung, HS: hsjung@yuhs.acen_US
dc.identifier.authorityJung, HS=rp01683en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.ydbio.2012.02.020en_US
dc.identifier.pmid22387209-
dc.identifier.scopuseid_2-s2.0-84862829863en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84862829863&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume365en_US
dc.identifier.issue1en_US
dc.identifier.spage259en_US
dc.identifier.epage266en_US
dc.identifier.isiWOS:000303030400024-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridCho, KW=7403956665en_US
dc.identifier.scopusauthoridKwon, HJ=18836582500en_US
dc.identifier.scopusauthoridShin, JO=37361704500en_US
dc.identifier.scopusauthoridLee, JM=41361401200en_US
dc.identifier.scopusauthoridCho, SW=32967447200en_US
dc.identifier.scopusauthoridTickle, C=7005294923en_US
dc.identifier.scopusauthoridJung, HS=7403030195en_US
dc.identifier.citeulike10400856-

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