Notch Regulates Cell Fate in the Developing Pronephros

Dev Biol. 2000 Nov 15;227(2):567-80. doi: 10.1006/dbio.2000.9913.

Abstract

The mechanisms that regulate cell fate within the pronephros are poorly understood but are important for the subsequent development of the urogenital system and show many similarities to nephrogenesis in the definitive kidney. Dynamic expression of Notch-1, Serrate-1, and Delta-1 in the developing Xenopus pronephros suggests a role for this pathway in cell fate segregation. Misactivation of Notch signaling using conditionally active forms of either Notch-1 or RBP-J/Su(H) proteins prevented normal duct formation and the proper expression of genetic markers of duct cell differentiation. Inhibition of endogenous Notch signaling elicited the opposite effect. Taken together with the mRNA expression patterns, these data suggest that endogenous Notch signaling functions to inhibit duct differentiation in the dorsoanterior region of the anlage where cells are normally fated to form tubules. In addition, elevated Notch signaling in the pronephric anlage both perturbed the characteristic pattern of the differentiated tubule network and increased the expression of early markers of pronephric precursor cells, Pax-2 and Wilms' tumor suppressor gene (Wt-1). We propose that Notch signaling plays a previously unrecognized role in the early selection of duct and tubule cell fates as well as functioning subsequently to control tubule cell patterning and development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Evolution
  • Calcium-Binding Proteins
  • Cell Differentiation
  • Drosophila Proteins*
  • Gene Expression Regulation, Developmental
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Kidney / embryology*
  • Kidney / metabolism
  • Kidney Tubules / embryology
  • Kidney Tubules / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Proteins / genetics
  • Receptors, Notch
  • Repressor Proteins / genetics
  • Serrate-Jagged Proteins
  • Signal Transduction
  • Xenopus Proteins
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics

Substances

  • Calcium-Binding Proteins
  • Drosophila Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Membrane Proteins
  • Proteins
  • Receptors, Notch
  • Repressor Proteins
  • Ser protein, Drosophila
  • Serrate-Jagged Proteins
  • Su(H) protein, Drosophila
  • Xenopus Proteins
  • delta protein
  • jag1 protein, Xenopus