scholarly journals Prep1 (pKnox1) transcription factor contributes to pubertal mammary gland branching morphogenesis

2018 ◽  
Vol 62 (11-12) ◽  
pp. 827-836 ◽  
Author(s):  
Lara Sicouri ◽  
Federica Pisati ◽  
Salvatore Pece ◽  
Francesco Blasi ◽  
Elena Longobardi
Keyword(s):  
Transcription Factor ◽  
Mammary Gland ◽  
Progenitor Cells ◽  
Mammary Gland Development ◽  
Branching Morphogenesis ◽  
Mouse Mammary Gland ◽  
Mammary Stem ◽  
Gland Development

Prep1 (pKnox1) is a homeodomain transcription factor essential for in utero and post-natal development and an oncosuppressor gene in human and adult mice. We have analyzed its role in the development of the mouse mammary gland. We used Prep1i/i hypomorphic and Prep1F/F-Ker5CRE crosses to analyze the role of Prep1 in vivo in adult mouse mammary gland development. We also cultured mammary gland stem/progenitor cells in mammospheres to perform biochemical studies. Prep1 was expressed in mammary gland progenitors and fully differentiated mammary gland cells. Using different Prep1-deficient mouse models we show that in vivo Prep1 contributes to mammary gland branching since the branching efficiency of the mammary gland in Prep1-deleted or Prep1 hypomorphic mice was largely reduced. In-vitro, Prep1 sustained functions of the mammary stem/progenitor compartment. Prep1-deficient mammary stem/progenitor cells showed reduced ability to form mammospheres; they were not able to branch in a 3D assay, and exhibited reduced expression of Snail1, Snail2 and vimentin. The branching phenotype associated with increased Tp53-dependent apoptosis and inability to properly activate signals involved in branching morphogenesis. Finally, Prep1 formed complexes with Snail2, a transcription factor essential in branching morphogenesis, and its absence destabilizes and promotes Snail2 proteasome-mediated degradation. We conclude that Prep1 is required for normal adult mammary gland development, in particular at its branching morphogenesis step. By binding Snail2, Prep1 protects it from the proteasomal degradation.

scholarly journals Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium

2000 ◽  
Vol 113 (12) ◽  
pp. 2129-2138 ◽  
Author(s):  
S. Naylor ◽  
M.J. Smalley ◽  
D. Robertson ◽  
B.A. Gusterson ◽  
P.A. Edwards ◽  
...  
Keyword(s):  
Cell Culture ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Ectopic Expression ◽  
Mammary Epithelium ◽  
Mouse Mammary Gland ◽  
Normal Mammary Gland ◽  
Gland Development

Several Wnt genes are expressed in the postnatal mouse mammary gland and are thought to be involved in mammary gland development. Ectopic expression of Wnt-1, which is not normally expressed in the mammary gland, drives the formation of a pre-neoplastic hyperplasia. Cell culture-based assays have shown that Wnt-1 and some mammary-expressed Wnts transform C57MG cells. This has led to the suggestion that Wnt-1 functions as an oncogene through the inappropriate activation of developmental events that are normally controlled by the ‘transforming’ class of Wnts. In this study, Wnt-7b was expressed in vivo using recombinant retroviruses. Wnt-7b did not alter normal mammary gland development despite having similar effects to Wnt-1 in cell culture. We conclude that the in vitro classification of Wnts as ‘transforming’ does not correlate with the transformation in vivo. To facilitate the analysis of Wnt-expression, a lacZ-containing, bicistronic recombinant retrovirus was developed. Immunohistochemistry and electron microscopy identified retrovirally transduced myoepithelial and luminal epithelial cells in normal and hyperplastic tissues. The distribution of transduced cells in mammary outgrowths was consistent with current models of mammary stem cell identity.

scholarly journals Notch3 marks clonogenic mammary luminal progenitor cells in vivo

2013 ◽  
Vol 203 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Daniel Lafkas ◽  
Veronica Rodilla ◽  
Mathilde Huyghe ◽  
Larissa Mourao ◽  
Hippokratis Kiaris ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Progenitor Cells ◽  
Mammary Gland Development ◽  
Notch Signaling Pathway ◽  
Luminal Progenitor ◽  
Mammary Stem ◽  
Luminal Progenitor Cells ◽  
Elevated Expression ◽  
Gland Development

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

Foxp3 heterozygosity does not overtly affect mammary gland development during puberty or the oestrous cycle in mice

2020 ◽  
Vol 32 (8) ◽  
pp. 774
Author(s):  
Vahid Atashgaran ◽  
Pallave Dasari ◽  
Leigh J. Hodson ◽  
Andreas Evdokiou ◽  
Simon C. Barry ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Cancer Susceptibility ◽  
Branching Morphogenesis ◽  
Genetic Mutation ◽  
Oestrous Cycle ◽  
Normal Mammary Gland ◽  
Foxp3 Mrna ◽  
Gland Development

Female mice heterozygous for a genetic mutation in transcription factor forkhead box p3 (Foxp3) spontaneously develop mammary cancers; however, the underlying mechanism is not well understood. We hypothesised that increased cancer susceptibility is associated with an underlying perturbation in mammary gland development. The role of Foxp3 in mammary ductal morphogenesis was investigated in heterozygous Foxp3Sf/+ and wildtype Foxp3+/+ mice during puberty and at specific stages of the oestrous cycle. No differences in mammary ductal branching morphogenesis, terminal end bud formation or ductal elongation were observed in pubertal Foxp3Sf/+ mice compared with Foxp3+/+ mice. During adulthood, all mice underwent normal regular oestrous cycles. No differences in epithelial branching morphology were detected in mammary glands from mice at the oestrus, metoestrus, dioestrus and pro-oestrus stages of the cycle. Furthermore, abundance of Foxp3 mRNA and protein in the mammary gland and lymph nodes was not altered in Foxp3Sf/+ mice compared with Foxp3+/+ mice. These studies suggest that Foxp3 heterozygosity does not overtly affect mammary gland development during puberty or the oestrous cycle. Further studies are required to dissect the underlying mechanisms of increased mammary cancer susceptibility in Foxp3Sf/+ heterozygous mice and the function of this transcription factor in normal mammary gland development.

scholarly journals DC-SCRIPT deficiency delays mouse mammary gland development and branching morphogenesis

2019 ◽  
Vol 455 (1) ◽  
pp. 42-50
Author(s):  
Chunling Tang ◽  
Renske J.E. van den Bijgaart ◽  
Maaike W.G. Looman ◽  
Nina Tel-Karthaus ◽  
Annemarie M.A. de Graaf ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Branching Morphogenesis ◽  
Mouse Mammary Gland ◽  
Gland Development

scholarly journals The Gli2 Transcription Factor Is Required for Normal Mouse Mammary Gland Development

2001 ◽  
Vol 238 (1) ◽  
pp. 133-144 ◽  
Author(s):  
Michael T. Lewis ◽  
Sarajane Ross ◽  
Phyllis A. Strickland ◽  
Charles W. Sugnet ◽  
Elsa Jimenez ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mammary Gland ◽  
Normal Mouse ◽  
Mammary Gland Development ◽  
Mouse Mammary Gland ◽  
Gland Development

scholarly journals The Role of Csmd1 during Mammary Gland Development

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 162
Author(s):  
Samuel J. Burgess ◽  
Hannah Gibbs ◽  
Carmel Toomes ◽  
Patricia L. Coletta ◽  
Sandra M. Bell
Keyword(s):  
Mammary Gland ◽  
Mammary Gland Development ◽  
Expression Patterns ◽  
Development In Vitro ◽  
Duct Development ◽  
Gland Development ◽  
Ductal Development

The Cub Sushi Multiple Domains-1 (CSMD1) protein is a tumour suppressor which has been shown to play a role in regulating human mammary duct development in vitro. CSMD1 knockdown in vitro demonstrated increased cell proliferation, invasion and motility. However, the role of Csmd1 in vivo is poorly characterised when it comes to ductal development and is therefore an area which warrants further exploration. In this study a Csmd1 knockout (KO) mouse model was used to identify the role of Csmd1 in regulating mammary gland development during puberty. Changes in duct development and protein expression patterns were analysed by immunohistochemistry. This study identified increased ductal development during the early stages of puberty in the KO mice, characterised by increased ductal area and terminal end bud number at 6 weeks. Furthermore, increased expression of various proteins (Stat1, Fak, Akt, Slug/Snail and Progesterone receptor) was shown at 4 weeks in the KO mice, followed by lower expression levels from 6 weeks in the KO mice compared to the wild type mice. This study identifies a novel role for Csmd1 in mammary gland development, with Csmd1 KO causing significantly more rapid mammary gland development, suggesting an earlier adult mammary gland formation.

scholarly journals The Pea3 Ets transcription factor regulates differentiation of multipotent progenitor cells during mammary gland development

2009 ◽  
Vol 325 (1) ◽  
pp. 106-121 ◽  
Author(s):  
Natasza A. Kurpios ◽  
Lesley MacNeil ◽  
Trevor G. Shepherd ◽  
David W. Gludish ◽  
Andrew O. Giacomelli ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mammary Gland ◽  
Progenitor Cells ◽  
Mammary Gland Development ◽  
Multipotent Progenitor Cells ◽  
Ets Transcription Factor ◽  
Gland Development
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