Expression of Notch receptors, ligands, and target genes during development of the mouse mammary gland

J Cell Physiol. 2011 Jul;226(7):1940-52. doi: 10.1002/jcp.22526.

Abstract

Notch genes play a critical role in mammary gland growth, development and tumorigenesis. In the present study, we have quantitatively determined the levels and mRNA expression patterns of the Notch receptor genes, their ligands and target genes in the postnatal mouse mammary gland. The steady state levels of Notch3 mRNA are the highest among receptor genes, Jagged1 and Dll3 mRNA levels are the highest among ligand genes and Hey2 mRNA levels are highest among expressed Hes/Hey target genes analyzed during different stages of postnatal mammary gland development. Using an immunohistochemical approach with antibodies specific for each Notch receptor, we show that Notch proteins are temporally regulated in mammary epithelial cells during normal mammary gland development in the FVB/N mouse. The loss of ovarian hormones is associated with changes in the levels of Notch receptor mRNAs (Notch2 higher and Notch3 lower) and ligand mRNAs (Dll1 and Dll4 are higher, whereas Dll3 and Jagged1 are lower) in the mammary gland of ovariectomized mice compared to intact mice. These data define expression of the Notch ligand/receptor system throughout development of the mouse mammary gland and help set the stage for genetic analysis of Notch in this context.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Calcium-Binding Proteins / genetics
  • Cell Line
  • Female
  • Gene Expression Regulation, Developmental*
  • Gonadal Steroid Hormones / metabolism
  • Immunohistochemistry
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / genetics
  • Jagged-1 Protein
  • Lactation / genetics
  • Ligands
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Knockout
  • Ovariectomy
  • Pregnancy
  • RNA Interference
  • RNA, Messenger / metabolism
  • Receptor, Notch2 / genetics
  • Receptor, Notch3
  • Receptors, Notch / genetics*
  • Receptors, Notch / metabolism
  • Repressor Proteins / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serrate-Jagged Proteins
  • Transfection

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • DLL4 protein, mouse
  • Dlk1 protein, mouse
  • Dll3 protein, mouse
  • Gonadal Steroid Hormones
  • Hey2 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Ligands
  • Membrane Proteins
  • Notch2 protein, mouse
  • Notch3 protein, mouse
  • RNA, Messenger
  • Receptor, Notch2
  • Receptor, Notch3
  • Receptors, Notch
  • Repressor Proteins
  • Serrate-Jagged Proteins