1. Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
2. Howard Hughes Medical Institute, Weill Graduate School of Medical Sciences, Cornell University, 445 East 69th Street, New York, New York 10021, USA
3. Neuroscience Program, Weill Graduate School of Medical Sciences, Cornell University, 445 East 69th Street, New York, New York 10021, USA
4. Molecular Cell and Developmental Biology Program; Weill Graduate School of Medical Sciences, Cornell University, 445 East 69th Street, New York, New York 10021, USA
5. Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA

Correspondence to: Kathryn V. Anderson¹ Email: k-anderson@ski.mskcc.org
The wim complementary DNA sequence is deposited in GenBank under accession number AY339616.

Abstract

Intraflagellar transport (IFT) proteins were first identified as essential factors for the growth and maintenance of flagella in the single-celled alga Chlamydomonas reinhardtii¹. In a screen for embryonic patterning mutations induced by ethylnitrosourea, here we identify two mouse mutants, wimple (wim) and flexo (fxo), that lack ventral neural cell types and show other phenotypes characteristic of defects in Sonic hedgehog signalling. Both mutations disrupt IFT proteins: the wim mutation is an allele of the previously uncharacterized mouse homologue of IFT172; and fxo is a new hypomorphic allele of polaris, the mouse homologue of IFT88. Genetic analysis shows that Wim, Polaris and the IFT motor protein Kif3a are required for Hedgehog signalling at a step downstream of Patched1 (the Hedgehog receptor) and upstream of direct targets of Hedgehog signalling. Our data show that IFT machinery has an essential and vertebrate-specific role in Hedgehog signal transduction.