Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development.
The formation of the dorsoventral (DV) boundary is central to establishing the body plan in embryonic development. Although there is some information about how limbs are positioned along the DV axis and how DV skin color pattern is determined, the way in which mammary glands are positioned is unknown. Here we focus on Bmp4 and Tbx3, a gene associated with ulnar-mammary syndrome, and compare their expression along the DV axis in relation to mammary gland initiation in mouse embryos. Tbx3 is expressed in the mammary gland-forming region with Tbx15, a gene involved in a DV coat color being expressed more dorsally and Bmp4 being expressed more ventrally. When Tbx3 was overexpressed, formation of mammary gland epithelium was extended along the DV axis. In contrast, overexpression of Bmp4 inhibited both Tbx3 and Tbx15 expression. In addition, when BMP signaling was inhibited by NOGGIN, Lef1 expression was lost. Thus, we propose that mutual interactions between Bmp4 and Tbx3 determine the presumptive DV boundary and formation of mammary glands in early mouse embryogenesis. 1,19-Dioctadecyl-3,3,39,39-tetramethyl indocarbocyanine perchloride labeling experiments showed that cells associated with mammary glands originate more dorsally and then move ventrally. This finding, together with previous findings, suggests that the same DV boundary may not only position limbs and determine coat color but also position mammary glands. Furthermore, Bmp signaling appears to be a fundamental feature of DV patterning.
Cho
Kyoung-Won
KW
Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea21 Project, College of Dentistry, Yonsei Center of Biotechnology, Yonsei University, Seoul 120-752, Korea.
Kim
Jae-Young
JY
Song
Soo-Jin
SJ
Farrell
Elizabeth
E
Eblaghie
Maxwell C
MC
Kim
Hee-Jin
HJ
Tickle
Cheryll
C
Jung
Han-Sung
HS
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002352:Carrier Proteins / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D017403:In Situ Hybridization; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009924:Organ Culture Techniques; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics*; D051153:Wnt Proteins / Q000235:genetics; D000099176:Noggin Protein
D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D020825:T-Box Domain Proteins; D051153:Wnt Proteins; D000099176:Noggin Protein; C525810:Bmp4 protein, mouse; C497574:Lef1 protein, mouse; C491460:Tbx3 protein, mouse; C102068:Wnt10b protein, mouse