Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland

Luigi Strizzi, Mario Mancino, Caterina Bianco, Ahmed Raafat, Monica Gonzales, Brian W. Booth, Kazuhide Watanabe, Tadahiro Nagaoka, David L. Mack, Beatrice Howard, Robert Callahan, Gilbert H. Smith, David S. Salomon

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Netrin-1 has been shown to regulate the function of the EGF-like protein Cripto-1 (Cr-1) and affect mammary gland development. Since Cr-1 is a target gene of Nanog and Oct4, we investigated the relationship between Netrin-1 and Cr-1, Nanog and Oct4 during different stages of development in the mouse mammary gland. Results from histological analysis show that exogenous Netrin-1 was able to induce formation of alveolar-like structures within the mammary gland terminal end buds of virgin transgenic Cripto-1 mice and enhance mammary gland alveologenesis in early pregnant FVB/N mice. Results from immunostainingand Western blot analysis show that Netrin-1, Nanog and Oct4 are expressed in the mouse embryonic mammary anlage epithelium while Cripto-1 is predominantly expressed outside this structure in the surrounding mesenchyme. We find that in lactating mammary glands of postnatal FVB/N mice, Netrin-1 expression is highest while Cripto-1 and Nanog levels are lowest indicating that Netrin-1 may perform a role in the mammary gland during lactation. HC-11 mouse mammary epithelial cells stimulated with lactogenic hormones and exogenous soluble Netrin-1 showed increased beta-casein expression as compared to control thus supporting the potential role for Netrin-1 during functional differentiation of mouse mammary epithelial cells. Finally, mouse ES cells treated with exogenous soluble Netrin-1 showed reduced levels of Nanog and Cripto-1 and higher levels of beta-III tubulin during differentiation. These results suggest that Netrin-1 may facilitate functional differentiation of mammary epithelial cells and possibly affect the expression of Nanog and/or Cripto-1 in multipotent cells that may reside in the mammary gland.

Original languageEnglish
Pages (from-to)824-834
Number of pages11
JournalJournal of Cellular Physiology
Volume216
Issue number3
DOIs
Publication statusPublished - 01-09-2008
Externally publishedYes

Fingerprint

Human Mammary Glands
Morphogenesis
Breast
Epithelial Cells
netrin-1
Mesoderm
Tubulin
Caseins
Lactation
Epidermal Growth Factor
Epithelium
Genes
Western Blotting
Hormones

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Strizzi, L., Mancino, M., Bianco, C., Raafat, A., Gonzales, M., Booth, B. W., ... Salomon, D. S. (2008). Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland. Journal of Cellular Physiology, 216(3), 824-834. https://doi.org/10.1002/jcp.21462
Strizzi, Luigi ; Mancino, Mario ; Bianco, Caterina ; Raafat, Ahmed ; Gonzales, Monica ; Booth, Brian W. ; Watanabe, Kazuhide ; Nagaoka, Tadahiro ; Mack, David L. ; Howard, Beatrice ; Callahan, Robert ; Smith, Gilbert H. ; Salomon, David S. / Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland. In: Journal of Cellular Physiology. 2008 ; Vol. 216, No. 3. pp. 824-834.
@article{c8aab4fd997044f4805a89a0adbb0732,
title = "Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland",
abstract = "Netrin-1 has been shown to regulate the function of the EGF-like protein Cripto-1 (Cr-1) and affect mammary gland development. Since Cr-1 is a target gene of Nanog and Oct4, we investigated the relationship between Netrin-1 and Cr-1, Nanog and Oct4 during different stages of development in the mouse mammary gland. Results from histological analysis show that exogenous Netrin-1 was able to induce formation of alveolar-like structures within the mammary gland terminal end buds of virgin transgenic Cripto-1 mice and enhance mammary gland alveologenesis in early pregnant FVB/N mice. Results from immunostainingand Western blot analysis show that Netrin-1, Nanog and Oct4 are expressed in the mouse embryonic mammary anlage epithelium while Cripto-1 is predominantly expressed outside this structure in the surrounding mesenchyme. We find that in lactating mammary glands of postnatal FVB/N mice, Netrin-1 expression is highest while Cripto-1 and Nanog levels are lowest indicating that Netrin-1 may perform a role in the mammary gland during lactation. HC-11 mouse mammary epithelial cells stimulated with lactogenic hormones and exogenous soluble Netrin-1 showed increased beta-casein expression as compared to control thus supporting the potential role for Netrin-1 during functional differentiation of mouse mammary epithelial cells. Finally, mouse ES cells treated with exogenous soluble Netrin-1 showed reduced levels of Nanog and Cripto-1 and higher levels of beta-III tubulin during differentiation. These results suggest that Netrin-1 may facilitate functional differentiation of mammary epithelial cells and possibly affect the expression of Nanog and/or Cripto-1 in multipotent cells that may reside in the mammary gland.",
author = "Luigi Strizzi and Mario Mancino and Caterina Bianco and Ahmed Raafat and Monica Gonzales and Booth, {Brian W.} and Kazuhide Watanabe and Tadahiro Nagaoka and Mack, {David L.} and Beatrice Howard and Robert Callahan and Smith, {Gilbert H.} and Salomon, {David S.}",
year = "2008",
month = "9",
day = "1",
doi = "10.1002/jcp.21462",
language = "English",
volume = "216",
pages = "824--834",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "3",

}

Strizzi, L, Mancino, M, Bianco, C, Raafat, A, Gonzales, M, Booth, BW, Watanabe, K, Nagaoka, T, Mack, DL, Howard, B, Callahan, R, Smith, GH & Salomon, DS 2008, 'Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland', Journal of Cellular Physiology, vol. 216, no. 3, pp. 824-834. https://doi.org/10.1002/jcp.21462

Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland. / Strizzi, Luigi; Mancino, Mario; Bianco, Caterina; Raafat, Ahmed; Gonzales, Monica; Booth, Brian W.; Watanabe, Kazuhide; Nagaoka, Tadahiro; Mack, David L.; Howard, Beatrice; Callahan, Robert; Smith, Gilbert H.; Salomon, David S.

In: Journal of Cellular Physiology, Vol. 216, No. 3, 01.09.2008, p. 824-834.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland

AU - Strizzi, Luigi

AU - Mancino, Mario

AU - Bianco, Caterina

AU - Raafat, Ahmed

AU - Gonzales, Monica

AU - Booth, Brian W.

AU - Watanabe, Kazuhide

AU - Nagaoka, Tadahiro

AU - Mack, David L.

AU - Howard, Beatrice

AU - Callahan, Robert

AU - Smith, Gilbert H.

AU - Salomon, David S.

PY - 2008/9/1

Y1 - 2008/9/1

N2 - Netrin-1 has been shown to regulate the function of the EGF-like protein Cripto-1 (Cr-1) and affect mammary gland development. Since Cr-1 is a target gene of Nanog and Oct4, we investigated the relationship between Netrin-1 and Cr-1, Nanog and Oct4 during different stages of development in the mouse mammary gland. Results from histological analysis show that exogenous Netrin-1 was able to induce formation of alveolar-like structures within the mammary gland terminal end buds of virgin transgenic Cripto-1 mice and enhance mammary gland alveologenesis in early pregnant FVB/N mice. Results from immunostainingand Western blot analysis show that Netrin-1, Nanog and Oct4 are expressed in the mouse embryonic mammary anlage epithelium while Cripto-1 is predominantly expressed outside this structure in the surrounding mesenchyme. We find that in lactating mammary glands of postnatal FVB/N mice, Netrin-1 expression is highest while Cripto-1 and Nanog levels are lowest indicating that Netrin-1 may perform a role in the mammary gland during lactation. HC-11 mouse mammary epithelial cells stimulated with lactogenic hormones and exogenous soluble Netrin-1 showed increased beta-casein expression as compared to control thus supporting the potential role for Netrin-1 during functional differentiation of mouse mammary epithelial cells. Finally, mouse ES cells treated with exogenous soluble Netrin-1 showed reduced levels of Nanog and Cripto-1 and higher levels of beta-III tubulin during differentiation. These results suggest that Netrin-1 may facilitate functional differentiation of mammary epithelial cells and possibly affect the expression of Nanog and/or Cripto-1 in multipotent cells that may reside in the mammary gland.

AB - Netrin-1 has been shown to regulate the function of the EGF-like protein Cripto-1 (Cr-1) and affect mammary gland development. Since Cr-1 is a target gene of Nanog and Oct4, we investigated the relationship between Netrin-1 and Cr-1, Nanog and Oct4 during different stages of development in the mouse mammary gland. Results from histological analysis show that exogenous Netrin-1 was able to induce formation of alveolar-like structures within the mammary gland terminal end buds of virgin transgenic Cripto-1 mice and enhance mammary gland alveologenesis in early pregnant FVB/N mice. Results from immunostainingand Western blot analysis show that Netrin-1, Nanog and Oct4 are expressed in the mouse embryonic mammary anlage epithelium while Cripto-1 is predominantly expressed outside this structure in the surrounding mesenchyme. We find that in lactating mammary glands of postnatal FVB/N mice, Netrin-1 expression is highest while Cripto-1 and Nanog levels are lowest indicating that Netrin-1 may perform a role in the mammary gland during lactation. HC-11 mouse mammary epithelial cells stimulated with lactogenic hormones and exogenous soluble Netrin-1 showed increased beta-casein expression as compared to control thus supporting the potential role for Netrin-1 during functional differentiation of mouse mammary epithelial cells. Finally, mouse ES cells treated with exogenous soluble Netrin-1 showed reduced levels of Nanog and Cripto-1 and higher levels of beta-III tubulin during differentiation. These results suggest that Netrin-1 may facilitate functional differentiation of mammary epithelial cells and possibly affect the expression of Nanog and/or Cripto-1 in multipotent cells that may reside in the mammary gland.

UR - http://www.scopus.com/inward/record.url?scp=48749127306&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48749127306&partnerID=8YFLogxK

U2 - 10.1002/jcp.21462

DO - 10.1002/jcp.21462

M3 - Article

VL - 216

SP - 824

EP - 834

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 3

ER -

Strizzi L, Mancino M, Bianco C, Raafat A, Gonzales M, Booth BW et al. Netrin-1 can affect morphogenesis and differentiation of the mouse mammary gland. Journal of Cellular Physiology. 2008 Sep 1;216(3):824-834. https://doi.org/10.1002/jcp.21462