MCSF orchestrates branching morphogenesis in developing submandibular gland tissue

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The importance of macrophages in tissue development and regeneration has been strongly emphasized. However, the specific roles of macrophage colony-stimulating factor (MCSF), the key regulator of macrophage differentiation, in glandular tissue development have been unexplored. Here, we disclose new macrophage-independent roles of MCSF in tissue development. We initially found that MCSF is markedly upregulated at embryonic day (E)13.5, at a stage preceding the colonization of macrophages (at E15.5), in mouse submandibular gland (SMG) tissue. Surprisingly, MCSF-induced branching morphogenesis was based on a direct effect on epithelial cells, as well as indirectly, by modulating the expression of major growth factors of SMG growth, FGF7 and FGF10, via the phosphoinositide 3-kinase (PI3K) pathway. Additionally, given the importance of neurons in SMG organogenesis, we found that MCSF-induced SMG growth was associated with regulation of neurturin expression and neuronal network development during early SMG development in an in vitro organogenesis model as well as in vivo. These results indicate that MCSF plays pleiotropic roles and is an important regulator of early SMG morphogenesis.

Original languageEnglish
Pages (from-to)1559-1569
Number of pages11
JournalJournal of Cell Science
Volume130
Issue number9
DOIs
Publication statusPublished - May 1 2017

Fingerprint

Macrophage Colony-Stimulating Factor
Submandibular Gland
Morphogenesis
Macrophages
Organogenesis
Neurturin
1-Phosphatidylinositol 4-Kinase
Growth
Regeneration
Intercellular Signaling Peptides and Proteins
Epithelial Cells
Neurons

Keywords

  • 3D culture
  • Branching morphogenesis
  • Fibroblast growth factor
  • Macrophage colony-stimulating factor
  • Neurturin
  • Salivary gland

ASJC Scopus subject areas

  • Cell Biology

Cite this

MCSF orchestrates branching morphogenesis in developing submandibular gland tissue. / Sathi, Gulsan Ara; Farahat, Mahmoud; Hara, Emilio satoshi; Taketa, Hiroaki; Nagatsuka, Hitoshi; Kuboki, Takuo; Matsumoto, Takuya.

In: Journal of Cell Science, Vol. 130, No. 9, 01.05.2017, p. 1559-1569.

Research output: Contribution to journalArticle

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AU - Kuboki, Takuo

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