Netrin-1 expression in fetal and regenerating rat pancreas and its effect on the migration of human pancreatic duct and porcine islet precursor cells

Diabetologia. 2003 Jul;46(7):926-33. doi: 10.1007/s00125-003-1125-5. Epub 2003 Jun 18.


Aims/hypothesis: We investigated the expression and function of netrin-1, a diffusible laminin-like protein known to regulate neuronal-cell migration in the pancreas. We questioned whether this factor regulates migration of pancreatic epithelial cells and whether this could be involved in islet neogenesis.

Methods: We studied fetal and adult rat pancreas wherein duct ligation induced islet neogenesis. Netrin-1 expression was analysed by RT-PCR, western blot and immunohistochemistry. In vitro cell migration was measured with a human pancreatic duct cell line (CAPAN-2) and with fetal porcine islet cells. We also studied the expression of two netrin-receptors, neogenin and deleted in colorectal cancer.

Results: We found a transient expression of netrin-1 mRNA and protein in fetal pancreas from E15 to E18, and in adult pancreas after duct ligation. In normal adult pancreas there was very little netrin-1 expression. Netrin-1 expression was observed both in endocrine and exocrine cells. At the immunohistochemical level, it was expressed by islet cells during tissue regeneration. We could show that netrin-1 increases the migration of fetal islet cells and of a ductal cell line, mainly via a chemokinetic effect. From the two well-established netrin receptors, DCC and neogenin, we only found neogenin to be expressed in the pancreas. Neogenin expression coincided with the period of netrin-1 up-regulation.

Conclusion/interpretation: Netrin-1 is involved in pancreatic morphogenesis and tissue remodelling and plays a role in the regulation of duct-cell and fetal-islet cell migration. This can be of importance in islet regeneration, where migration of islet precursors takes place.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • DNA Primers
  • Gene Expression Regulation
  • Immunohistochemistry
  • Insulin / metabolism
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / embryology
  • Islets of Langerhans / physiology
  • Male
  • Membrane Proteins / metabolism
  • Nerve Growth Factors / genetics*
  • Netrin-1
  • Pancreas / embryology
  • Pancreas / physiology*
  • Pancreatic Ducts / physiology*
  • Rats
  • Rats, Wistar
  • Regeneration / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / physiology
  • Swine
  • Tumor Suppressor Proteins


  • DNA Primers
  • Insulin
  • Membrane Proteins
  • NTN1 protein, human
  • Nerve Growth Factors
  • Ntn1 protein, rat
  • Tumor Suppressor Proteins
  • neogenin
  • Netrin-1