Elsevier

Developmental Biology

Volume 255, Issue 1, 1 March 2003, Pages 178-191
Developmental Biology

Regular article
Role of PI 3-kinase and PIP3 in submandibular gland branching morphogenesis

https://doi.org/10.1016/S0012-1606(02)00047-7Get rights and content
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Abstract

The mouse submandibular gland (SMG) epithelium undergoes extensive morphogenetic branching during embryonic development as the first step in the establishment of its glandular structure. However, the specific signaling pathways required for SMG branching morphogenesis are not well understood. Using E13 mouse SMG organ cultures, we showed that inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), wortmannin and LY294002, substantially inhibited branching morphogenesis in SMG. Branching morphogenesis of epithelial rudiments denuded of mesenchyme was inhibited similarly, indicating that PI 3-kinase inhibitors act directly on the epithelium. Immunostaining and Western analysis demonstrated that the p85 isoform of PI 3-kinase is expressed in epithelium at levels higher than in the mesenchyme. A target of PI 3-kinase, Akt/protein kinase B (PKB), showed decreased phosphorylation at Ser473 by Western analysis in the presence of PI 3-kinase inhibitors. The major lipid product of PI 3-kinase, phosphatidylinositol 3,4,5-trisphosphate (PIP3), was added exogenously to SMG via a membrane-transporting carrier in the presence of PI 3-kinase inhibitors and was found to stimulate cleft formation, the first step of branching morphogenesis. Together, these data indicate that PI 3-kinase plays a role in the regulation of epithelial branching morphogenesis in mouse SMG acting through a PIP3 pathway.

Keywords

Branching morphogenesis
Salivary gland
Submandibular gland
Organ culture
Phosphatidylinositol 3-kinase
Phosphatidylinositol 3,4,5-trisphosphate
Akt
Inhibitors
Mouse
Time-lapse microscopy

Cited by (0)

1

Present address: School of Dentistry, Medical College of Virginia Campus, Virginia Commonwealth University, Box 980566, Richmond, VA 23298-0566, USA.

2

Present address: Department of Cell Biology & Anatomy, College of Dental Medicine, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA.