+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

The mouse mammary gland requires the actin-binding protein gelsolin for proper ductal morphogenesis



The mouse mammary gland requires the actin-binding protein gelsolin for proper ductal morphogenesis



Developmental Biology 225(2): 407-423



Gelsolin is an actin-binding/severing protein expressed in intracellular and secreted forms. It is a major regulator of the form and function of the actin cytoskeleton in most all cells. Here we demonstrate that female mice with a targeted deletion of the gelsolin gene (Gsn-/-) have defects in mammary gland morphogenesis. Two distinct defects were identified in the gelsolin-null mammary gland. First, the mammary anlage from Gsn-/- mice failed to elongate at the onset of puberty and remained rudimentary until approximately 9 weeks of age, early block (Gsn-/-(EB)). Second, after the mammary epithelium had filled the mammary fat pad, a complete lack of terminal branching, or late block, was observed (Gsn-/-(LB)). The Gsn-/-(EB) was seen in 70% of Gsn-/- mice and appeared to be dependent on a modifier gene(s) in addition to the loss of gelsolin. Gsn-/-(LB) was observed in all Gsn-/- mice. Terminal end buds (TEBs) were not evident in the mammary anlage from Gsn-/-(EB) mice until approximately 9 weeks of age. Cellular proliferation in the terminal ductal regions of Gsn-/-(EB) females was detected by bromodeoxyuridine incorporation, but was less than that found in the TEBs of age-matched controls. In mice deficient for gelsolin, mammary gland architecture was unaltered at the histological level. Lobuloalveolar development was delayed in response to pregnancy in mammary glands of Gsn-/- mice but was otherwise normal. Lactation and involution in the gelsolin-null animals were similar to those of wild-type mice. Transplantation of epithelium devoid of gelsolin into a wild-type (GsnWT) mammary fat pad resulted in proper arborization of the ductal tree. Transplantation of GsnWT epithelium into the Gsn-/- fat pad recapitulated the lack of terminal branching seen in Gsn-/- females. These results indicate that gelsolin is required in the mammary stroma for proper ductal morphogenesis. Our results provide the first evidence of an actin regulatory protein affecting mammary ductal growth through stromal-epithelial communication.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010008851

Download citation: RISBibTeXText

PMID: 10985859

DOI: 10.1006/dbio.2000.9844


Related references

ErbB3 is required for ductal morphogenesis in the mouse mammary gland. Breast Cancer Research 10(6): R96, 2009

Induction of ductal morphogenesis and lobular hyperplasia by amphiregulin in the mouse mammary gland. Cell Growth & Differentiation 7(12): 1769-1781, 1996

Milk protein expression and ductal morphogenesis in the mammary gland in vitro: hormone-dependent and -independent phases of adipocyte-mammary epithelial cell interaction. Developmental Biology 120(1): 245-258, 1987

Ductal morphogenesis in the mouse mammary gland evidence supporting a role for epidermal growth factor. Developmental Biology 127(2): 304-315, 1988

C/EBPb, but not C/EBPa, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland. Genes and Development 12(12): 17-28, 1998

C/EBPbeta, but not C/EBPalpha, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland. Genes and Development 12(12): 1917-1928, 1998

Hepatocyte growth factor-like protein is a positive regulator of early mammary gland ductal morphogenesis. Mechanisms of Development 133: 11-22, 2015

Transgenic mice overexpressing tgf alpha exhibit impeded ductal morphogenesis in the mammary gland and ductal metaplasia in the pancreas. Journal of Cellular Biochemistry Supplement (14 PART E): 79, 1990

Evidence for an actin binding helix in gelsolin segment 2; Have homologous sequences in segments 1 and 2 of gelsolin evolved to divergent actin binding functions?. Febs Letters. 397(2-3): 196, 1996

P190-B Rho GTPase-activating protein overexpression disrupts ductal morphogenesis and induces hyperplastic lesions in the developing mammary gland. Molecular Endocrinology 20(6): 1391-1405, 2006

Distinct roles of four gelsolin-like domains of Caenorhabditis elegans gelsolin-like protein-1 in actin filament severing, barbed end capping, and phosphoinositide binding. Biochemistry 49(20): 4349-4360, 2010

Flightless-I, a gelsolin related actin binding protein, increases its association with the actin cytoskeleton of activated platelets and modulates actin polymerization in vitro. Blood 88(10 SUPPL 1 PART 1-2): 439A, 1996

FOXC1 is enriched in the mammary luminal progenitor population, but is not necessary for mouse mammary ductal morphogenesis. Biology of Reproduction 89(1): 10, 2014

ErbB2 is required for ductal morphogenesis of the mammary gland. Proceedings of the National Academy of Sciences of the United States of America 101(49): 17138-17143, 2004