Involvement of axonal guidance proteins and their signaling partners in the developing mouse mammary gland

J Cell Physiol. 2006 Jan;206(1):16-24. doi: 10.1002/jcp.20427.


Mammary morphogenesis in the mouse is driven by specialized structures at the ends of the developing ducts, the terminal end buds (TEB). The mechanisms controlling the precise branching and spacing of the ducts are, as yet, unknown. To identify genes that are associated with migration of TEB and differentiation of the subtending ducts, we developed a novel method of isolating TEB and ducts free of stroma, and compared the gene expression profiles of these two isolates using oligonucleotide microarrays. Ninety one genes were upregulated in TEB compared to ducts. Three of these genes, Sprr1A, Sema3B, and BASP1, are associated with axonal growth and guidance. Two additional members of the Sprr family, Sprr2A and 2B, not previously associated with axonal growth, were also highly expressed in TEB. Expression of these genes was confirmed by RT-PCR and Western blotting, and the cellular distribution of Sprr1A and BASP1 was demonstrated by immunohistochemistry. Other semaphorins, including Sema3C, 4A, 4F and the cancer invasion associated Sema 4D were also expressed in the mouse mammary gland along with the semaphorin receptors, Plexins A2, A3, B2, and D1, and Neuropilins 1 and 2. These results are discussed in the context of other proteins expressed in the developing gland that are known to be downstream effectors of these signaling molecules. We suggest that these genes may influence ductal growth and morphogenesis in the developing mammary gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism*
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Movement / physiology
  • Cornified Envelope Proline-Rich Proteins
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • In Vitro Techniques
  • Mammary Glands, Animal* / anatomy & histology
  • Mammary Glands, Animal* / growth & development
  • Mammary Glands, Animal* / physiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Morphogenesis*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuropilins / genetics
  • Neuropilins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Semaphorins / genetics
  • Semaphorins / metabolism
  • Signal Transduction / physiology*


  • Basp1 protein, mouse
  • Calmodulin-Binding Proteins
  • Cell Adhesion Molecules
  • Cornified Envelope Proline-Rich Proteins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neuropilins
  • Protein Isoforms
  • Semaphorins
  • plexin