Inversin relays Frizzled-8 signals to promote proximal pronephros development.

Abstract:

:Mutations of inversin cause type II nephronophthisis, an infantile autosomal recessive disease characterized by cystic kidney disease and developmental defects. Inversin regulates Wnt signaling and is required for convergent extension movements during early embryogenesis. We now show that Inversin is essential for Xenopus pronephros formation, involving two distinct and opposing forms of cell movements. Knockdown of Inversin abrogated both proximal pronephros extension and distal tubule differentiation, phenotypes similar to that of Xenopus deficient in Frizzled-8. Exogenous Inversin rescued the pronephric defects caused by lack of Frizzled-8, indicating that Inversin acts downstream of Frizzled-8 in pronephros morphogenesis. Depletion of Inversin prevents the recruitment of Dishevelled in response to Frizzled-8 and impeded the accumulation of Dishevelled at the apical membrane of tubular epithelial cells in vivo. Thus, defective tubule morphogenesis seems to contribute to the renal pathology observed in patients with nephronophthisis type II.

authors

Lienkamp S,Ganner A,Boehlke C,Schmidt T,Arnold SJ,Schäfer T,Romaker D,Schuler J,Hoff S,Powelske C,Eifler A,Krönig C,Bullerkotte A,Nitschke R,Kuehn EW,Kim E,Burkhardt H,Brox T,Ronneberger O,Gloy J,Walz G

doi

10.1073/pnas.1013070107

subject

Has Abstract

pub_date

2010-11-23 00:00:00

pages

20388-93

issue

47

eissn

0027-8424

issn

1091-6490

pii

1013070107

journal_volume

107

pub_type

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