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Dev Biol November 15, 2000; 227 (2): 567-80.

Notch regulates cell fate in the developing pronephros.

McLaughlin KA , Rones MS , Mercola M .

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.

PubMed ID: 11071775
Article link: Dev Biol
Grant support: F32 HL09740-03 NHLBI NIH HHS , R01 HL59502 NHLBI NIH HHS

Genes referenced: dll1 jag1 lhx1 notch1 pax2 ret wt1

Antibodies referenced: Kidney Ab1

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