Tubulogenesis

Introduction

Tubulogenesis is synonymous with the term branching morphogenesis (i.e. the generation of a branching structure from a specific duct). Epithelial organs such as the kidney, lung, mammary glands, and salivary glands form by this process1,2. Tubulogenesis is not only conserved among different epithelial organs; its mechanisms are thought to be conserved throughout evolution3.

Cell Types Used

Tubulogenesis in kidney formation has been extensively studied4 and a very useful model system for its study has been the development of the Madin-Darby canine kidney (MDCK) cell line and the MDCK hepatocyte growth factor (HGF) in vitro assay. Briefly, the assay requires the three-dimensional collagen culture of MDCK cells which form a cyst after ten days, consisting of a polarized epithelium and a fluid-filled center. When the cysts are then exposed to HGF, the cysts form branching tubules which resembles in vivo branching morphogenesis in the kidney1.

Tubulogenesis in mammary and salivary glands and endothelial cells have also been described in collagen gels in three dimensions5-7.

References

  1. Helman NE et al, Matrix metalloproteinase 13 (MMP13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP1), regulated by the MAPK pathway, are both necessary for Madin-Darby Canine Kidney tubulogenesis J. Biol. Chem. (2008) 283: 4272-4282.
  2. Lopez JL et al, Biomechanical regulation of cell orientation and fate. Oncogene (2008) 27: 6981-6993.
    Medioni C et al, Genetic control of cell morphogenesis during Drosophila melanogaster cardiac tube formation J. Cell Biol (2008) 182:249-261.
  3. Stuart RO et al, Epithelial tubulogenesis through branching morphogenesis: relevance to collecting system development. J. Am. Soc. Nephrol. (1995) 6: 1151-1159.
  4. Daniel CW et al, Similar growth pattern of mouse mammary epithelium cultivated in collagen matrix in vivo and in vitro. Dev Biol. (1984) 104:57-64.
  5. Furue M et al, Effects of hepatocyte growth factor (HGF) and activin A on the morphogenesis of rat submandibular gland-derived epithelial cells in serum-free collagen gel culture. In Vitro Cell Dev Biol Anim. (1999) 35:131-5.
  6. Yang S et al, Functional roles for PECAM-1 (CD31) and VE-Cadherin (CD144) in tube assembly and lumen formation in three-dimensional collagen gels. Am J. Path (1999) 155: 887-895.