Morphogenesis of the developing mammary gland

Stage-dependent impact of adipocytes

Shira Landskroner-Eiger, Jiyoung Park, Davelene Israel, Jeffrey W. Pollard, Philipp E. Scherer

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Mammary gland development is critically dependent on the interactions between the stromal and the epithelial compartments within the gland. These events are under the control of a complex interplay of circulating and locally acting hormones and growth factors. To analyze the temporal and quantitative contributions of stromal adipocytes, we took advantage of the FAT-ATTAC mice (apoptosis through triggered activation of caspase-8), a model of inducible and reversible loss of adipocytes. This loss can be achieved through the induced dimerization of a caspase-8 fusion protein. In the context of female mice, we can achieve ablation of mammary adipocytes relatively selectively without affecting other fat pads. Under these conditions, we find that adipocytes are essential for the formation of the extended network of ducts in the mammary gland during puberty. Beyond their role in development, adipocytes are also essential to maintain the normal alveolar structures that develop during adulthood. Loss of adipose tissue initiated 2 weeks after birth triggers fewer duct branching points and fewer terminal end buds (TEBs) and also triggers changes in proliferation and apoptosis in the epithelium associated with the TEBs. The reduced developmental pace that adipocyte-ablated glands undergo is reversible, as the emergence of new local adipocytes, upon cessation of treatment, enables the ductal epithelium to resume growth. Conversely, loss of local adipocytes initiated at 7 weeks of age resulted in excessive lobulation, indicating that adipocytes are critically involved in maintaining proper architecture and functionality of the mammary epithelium. Collectively, using a unique model of inducible and reversible loss of adipocytes, our observations suggest that adipocytes are required for proper development during puberty and for the maintenance of the ductal architecture in the adult mammary gland.

Original languageEnglish (US)
Pages (from-to)968-978
Number of pages11
JournalDevelopmental Biology
Volume344
Issue number2
DOIs
StatePublished - Aug 2010

Fingerprint

Human Mammary Glands
Morphogenesis
Adipocytes
Epithelium
Caspase 8
Puberty
Adipose Tissue
Breast
Apoptosis
Withholding Treatment
Dimerization
Intercellular Signaling Peptides and Proteins
Maintenance
Parturition
Hormones

Keywords

  • Adipocytes
  • Mammary gland
  • Stroma

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology

Cite this

Morphogenesis of the developing mammary gland : Stage-dependent impact of adipocytes. / Landskroner-Eiger, Shira; Park, Jiyoung; Israel, Davelene; Pollard, Jeffrey W.; Scherer, Philipp E.

In: Developmental Biology, Vol. 344, No. 2, 08.2010, p. 968-978.

Research output: Contribution to journalArticle

Landskroner-Eiger, Shira ; Park, Jiyoung ; Israel, Davelene ; Pollard, Jeffrey W. ; Scherer, Philipp E. / Morphogenesis of the developing mammary gland : Stage-dependent impact of adipocytes. In: Developmental Biology. 2010 ; Vol. 344, No. 2. pp. 968-978.
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