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In conclusion, Notch signaling system dynamically varies throughout the development of the mammary gland during puberty pointing to specific time involvement of each component. Introduction It has been stated that the future milk yield potential of cows depends on the optimum development of the mammary parenchyma that is established during growth, starting as early as the first weeks of life 1 , 2.

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Before and around puberty the gland grows allometrically faster than the rest of the body , mainly in response of increasing estradiol and IGF1 levels 3. On the other hand, the parenchymal tissue of the gland is composed of epithelial structures and will be responsible for production and transport of the milk.

The mammary epithelium is composed of two layers of epithelial cells: luminal cells of cubical shape that line the hollow lumens of the ducts, surrounded by flat myoepithelial cells that have a contractile function. As the gland matures, branching and ductal elongation occur in response to endocrine and paracrine stimuli 4 , 5. It has been shown that nutrition plays an important role in regulating the growth of the bovine mammary gland in the early stages of development, specially pre weaning 6.

Efforts are now being directed to elucidate genes involved in this process 7 , 8. After puberty, the mammary gland undergoes repeated cycles of development and involution coordinated with pregnancy and lactation cycles. This process of growth and regression points to a hierarchy of stem and progenitor cells that are able to regenerate specialized populations of mammary epithelial and myoepithelial cells.

Over the last decades, evidence for the existence of mammary stem cells MaSC , capable of self-renewing and generating multiple mammary cell types has accumulated mainly in mice and humans, but also in bovines and other farm animal species 9 , 10 , 11 , Recently a cell lineage hierarchy has been proposed in the bovine mammary gland based on different stem cell markers 13 , and differential evolution of progenitor cell populations during lactation has been described Notch pathway is conserved from flies to mammals.

It regulates numerous cellular processes like cellular proliferation, differentiation, and apoptosis and has a relevant role in stem cell maintenance 15 , Notch signaling includes cell to cell interactions by means of receptors and ligands, anchored on cell membranes of neighboring cells.

The Notch intracellular domain NICD contains nuclear localization signals and the transcriptional activation domain The intracellular transduction of Notch signaling is remarkably simple, with no secondary messengers involved. This active domain translocates to the nucleus where it interacts with transcription factors to activate specific genes involved in proliferation, differentiation and survival The binding and function of NOTCH on DNA is a rapid and dynamic process controlled by phosphorylation, ubiquitination and subsequent proteasomal degradation, which shuts off the pathway.

In the absence of NICD, the transcription factor RBPJ Recombining binding protein suppressor of hairless forms complexes with a variety of corepressors to suppress the transcription of Notch target genes 20 , Many Notch target genes have been identified.

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The Notch signaling system has been shown to maintain precursor cells by balancing cellular proliferation, cell fate and differentiation in several tissues, such as brain, muscle, intestine and hematopoietic cells 23 , 24 , 25 , 26 , Notch pathway activity has been associated with stem cells in many tissues, and therefore it has been used to trace lineages in some tissues like the intestine and the mammary gland 9 , 28 , Recently, increasing amount of work has approached Notch signaling in the mammary gland to decipher the lineage hierarchies that contribute to mammary development, and understand the morphogenesis of the gland.

Furthermore new insights have linked the Notch system to the cellular origins of mammary tumors 15 , 30 , In cows, however, a paucity of studies have been performed on Notch signaling in the mammary gland 13 , During development, all four Notch receptor paralogues, NOTCH1—4, have been shown to be expressed in the mouse and the human mammary gland 33 , 34 , however no reports are yet found on Notch signaling in the pubertal bovine mammary gland.

With the perspective of understanding all insights of the regulation of mammary development during puberty which will impact on performance of the future gland in adulthood, we investigated the expression and localization of the four Notch receptor paralogues, as well as the expression of two ligands and three target genes in the bovine mammary gland before, during and after puberty onset.

Results We performed immunohistochemical labeling of the four Notch receptors in paraffin sections of biopsies of the mammary gland of Holstein heifers, taken at 20, 30, 40 and 70 weeks of age representative images are shown in Fig.


Notch labeling was positive for the four paralogues at all ages investigated. NOTCH1 was mostly found in epithelial and myoepithelial cells of the parenchyma though its presence was also evidenced in stromal cells. The label was identified at membrane, cytoplasmic and nuclear levels.

NOTCH2 was evidenced in parenchymal and stromal cells at cytoplasmic and nuclear levels, and it was predominantly found in the cytoplasm of epithelial and myoepithelial cells.

NOTCH3 was identified mostly in the cytoplasm of epithelial and myoepithelial cells and, with lesser intensity, in some stromal cells. The label of NOTCH4 was stronger in myoepithelial cells, and was predominantly nuclear, but it was also evidenced, with lesser intensity, at cytoplasmic level.

No particular age pattern of labeling could be evidenced with this technique for any of the four Notch receptor paralogues. In summary, the four Notch paralogues are present in both compartments, parenchyma and stroma, with the exception of NOTCH3 that is rarely expressed in stromal cells.

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Target Band 7 : IELTS Academic Module - How to Maximize Your Score

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Libraries ACT. With respect to NOTCH4, the proportion of its active form followed an opposite pattern during development, being maximal at 20 weeks of age prepubertally , and then minimal, during puberty and postpuberty, suggesting an earlier activation of this paralogue. Oct 02, Watyuyu rated it really liked it Shelves: There are no discussion topics on this book yet. Login to add to list.

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