Prenatal Morphogenesis of Mammary Glands in Mouse and Rabbit

Propper, Alain; Howard, Beatrice A.; Veltmaat, Jacqueline M.

doi:10.1007/s10911-013-9298-0

Cited by 45 publications

(56 citation statements)

References 66 publications

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“…The mammary gland is one of several well studied ductal systems that use branching mechanisms during development (Ochoa-Espinosa and Affolter 2012). In the mouse, mammary ductal development starts on embryonic day 11.5 with the formation of mammary lines that condense into five pairs of mammary placodes (Propper et al 2013). These placodes then go on to form rudimentary ductal trees which are each embedded in a stroma termed the mammary fat pad (Propper et al 2013; Sakakura et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…In the mouse, mammary ductal development starts on embryonic day 11.5 with the formation of mammary lines that condense into five pairs of mammary placodes (Propper et al 2013). These placodes then go on to form rudimentary ductal trees which are each embedded in a stroma termed the mammary fat pad (Propper et al 2013; Sakakura et al 2013). Although little development of the ductal tree occurs during the immediate postnatal period, the onset of puberty causes allometic expansion and arborization (Sternlicht 2006).…”

Section: Introductionmentioning

confidence: 99%

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In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

Hadsell

Olea

et al. 2015

Mamm Genome

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Genetic background plays a dominant role in mammary gland development and breast cancer (BrCa). Despite this, the role of genetic diversity in mammary gland development is only partially understood. This study used strain-dependent variation in an inbred mouse mapping panel, to identify quantitative trait loci (QTL) underlying structural variation in mammary ductal development, and determined if these QTL correlated with genomic intervals conferring breast cancer susceptibility in humans. For about half of the traits, the observed variation among the complete set of strains in this study was greater (P<0.05) than that observed with previously studied strains or with strains that are in current common use for mammary gland biology. Correlations were also detected with previously reported variation in mammary tumor latency and metastasis. In silico genome-wide association (GWAS) identified 20 mammary development QTL (Mdq). Of these, 5 were syntenic with previously reported human BrCa loci. The most highly significant (P=1×10 −11 ) association of the study was on MMU6 and contained the genes Plxna4, Plxna4os1, and Chchd3. On MMU5, a QTL was detected (p=8×10 −7 ) that was syntenic to a human BrCa locus on h12q24.5 containing the genes Tbx3 and Tbx5. Intersection of highassociation SNP (r 2 >0.8) with genomic and epigenomic features, and intersection of candidate genes with gene expression and survival data from human BrCa highlighted several for further study. These results support the conclusion that genetic variation in mammary ductal development is greater than previously appreciated. They also suggest that mammary tumor latency and metastatic index may be influenced by variations in the same factors that control normal mammary ductal development and that further studies of genetically diverse mice can improve our understanding of the connection between breast development and breast cancer in humans by identifying novel susceptibility genes. HHS Public Access

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

Hadsell

Olea

et al. 2015

Mamm Genome

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“…The failure of a signal that normally leads to s-SHIP-GFP progenitor cell aggregation along the mammary-forming region would explain the striking phenotypes observed uniquely with MP3 in Nrg3 ska mice [1]. The results presented here demonstrate the power of using the s-SHIP-GFP reporter model that permits analyses of epithelial progenitor cells through sequential developmental stages in situ using ex vivo embryonic cultures, which had not been previously possible for studies of embryonic mammary morphogenesis.…”

Section: Alterations In Epithelial Progenitor Cell Distributions Inmentioning

confidence: 82%

“…T he mammary primordium (MP) consists of the primitive mammary epithelium and the adjacent mesenchyme [1]. Together these two tissues will direct the formation of the mammary gland during embryogenesis through a series of reciprocal interactions in which juxtacrine and paracrine signals are transmitted to mediate morphogenetic processes [2].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have concluded that early mammary morphogenesis is primarily mediated via localized cell movements [15,17]. It is not yet clear which signals mobilize the epithelial progenitors that are thought to locally migrate from along and near the mammary line to form the MP [1]. Cell hypertrophy is also thought to contribute to increase in MP size [16].…”

Section: Introductionmentioning

confidence: 99%

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Neuregulin-3Regulates Epithelial Progenitor Cell Positioning and Specifies Mammary Phenotype

Kogata

Oliemuller

Wansbury

et al. 2014

Stem Cells and Development

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Mutation of Neuregulin-3 (Nrg3) results in defective embryonic mammary gland development. Here, we investigate functions of Nrg3 signaling in embryonic mammary morphogenesis. Nrg3 regulates the distribution of epithelial progenitor cells within the presumptive mammary-forming region during early mammary morphogenesis. Basal and suprabasal epithelial cells are significantly smaller within the hypoplastic mammary primordium (MP) that forms in Nrg3 mutants, indicative of failure to acquire mammary epithelial cell (MEC) morphological phenotype. Activation of Erbb4 JM-a CYT-1, an Erbb4 isoform expressed in the developing MP, leads to MEC spreading and migration. Nrg3 promotes the accumulation of epithelial progenitor cells at the MP site in embryo explant cultures. Our results implicate Nrg3 signaling in mediating key events of mammary mesenchyme specification, including mesenchymal condensation, mitosis, and induction of mammary marker expression. Taken together, our results show Nrg3 has a major role in conferring specification of the mammary phenotype to both epithelial and mesenchymal progenitor cells.

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Embryonic Mammary Gland Development

Tickle

Jung

2016

Encyclopedia of Life Sciences

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Mammary glands are derived from the ectoderm and are a defining feature of mammals. The number of glands that develop along the ‘mammary lines’ on either side of the ventral trunk depends on the mammalian species. The mesoderm specifies the position in which glands develop. Positional information is encoded by transcription factors and transmitted to overlying ectoderm by signalling molecules. Determination of the mammary epithelium arises from induction of transcription factors and signalling molecules. Signals from the mammary epithelium induce the underlying mesoderm to form the mammary mesenchyme required for further development. The gland initiates as a discrete placode which sinks into the mesoderm to form a bud; the bud then lengthens to form an elongated sprout, which undergoes branching morphogenesis in a pattern dictated by the mesoderm. The gland lining is generated by formation of the lumen, and bipotent mammary stem cells give rise to luminal epithelial and myoepithelial cells. Key Concepts Mammary glands develop along ‘mammary lines’ that run from axilla (anterior) to groin (posterior) along both right and left sides of the ventral aspect of the mammalian trunk. Ectoderm cells of the mammary line migrate and aggregate to form individual discrete mammary placodes. The precise location of the mammary line and the placodes in the ectoderm is controlled by signals from underlying mesodermal tissues. Signals that control the formation of the mammary line and placodes include members of the WNT, FGF, NEUREGULIN and BMP signalling pathways. The Hedgehog signalling pathway is also involved. The TBX3 transcription factor is essential for the formation of the mammary placodes in mouse embryos, and mutations in the TBX3 gene have been found in patients with Ulnar‐mammary syndrome. The epithelial cells of the mammary bud produce parathyroid hormone‐related protein, which induces nearby mesoderm to form the mammary mesenchyme. Interactions between the mammary epithelial cells and the mammary mesenchyme are essential for further development and the subsequent elongation of the mammary bud to form a mammary sprout, which then undergoes branching morphogenesis in a pattern dictated by the deeper mesenchyme. Formation of the lumen of the embryonic gland involves fusion of microlumina created by local development of nonadhesive surfaces on the mammary epithelial cells and generates the epithelial lining which consists of an inner layer of luminal cells and an outer layer of myoepithelial cells. The cells of the mammary placode are determined to give rise to mammary epithelial cells; in the mammary bud, mammary stem cells can be detected that can give rise to both luminal and myoepithelial cells. Parallels, such as invasiveness, exist between the development of embryonic mammary glands and breast tumours and many of same molecules are involved.

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Prenatal Morphogenesis of Mammary Glands in Mouse and Rabbit

Cited by 45 publications

References 66 publications

In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

Neuregulin-3Regulates Epithelial Progenitor Cell Positioning and Specifies Mammary Phenotype

Embryonic Mammary Gland Development

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