The hydrocephalus inducing gene product, Hydin, positions axonemal central pair microtubules.

Helen R Dawe,Helen Farr,Michael K Shaw,Keith Gull

doi:10.1186/1741-7007-5-33

Abstract

BackgroundImpairment of cilia and flagella function underlies a growing number of human genetic diseases. Mutations in hydin in hy3 mice cause lethal communicating hydrocephalus with early onset. Hydin was recently identified as an axonemal protein; however, its function is as yet unknown.ResultsHere we use RNAi in Trypanosoma brucei to address this issue and demonstrate that loss of Hydin causes slow growth and a loss of cell motility. We show that two separate defects in newly-formed flagellar central pair microtubules underlie the loss of cell motility. At early time-points after RNAi induction, the central pair becomes mispositioned, while at later time points the central pair is lost. While the basal body is unaffected, both defects originate at the basal plate, reflecting a role for TbHydin throughout the length of the central pair.ConclusionOur data provide the first evidence of Hydin's role within the trypanosome axoneme, and reveal central pair anomalies and thus impairment of ependymal ciliary motility as the likely cause of the hydrocephalus observed in the hy3 mouse.

Highlights

Impairment of cilia and flagella function underlies a growing number of human genetic diseases
We show that two separate defects in central pair microtubules underlie the loss of flagellar motility, revealing central pair anomalies and impairment of ependymal ciliary motility as the likely cause of the aetiology of this disease
Ablation of TbHydin causes slow growth and motility defects To provide a functional explanation for the hydrocephalus observed in hy3 mice, we cloned a 580 base pair fragment of the 5' end of the TbHydin gene (GeneDB accession number Tb927.6.3150) and used inducible RNAi in the single-celled model organism T. brucei to ablate protein expression

Summary

Introduction

Impairment of cilia and flagella function underlies a growing number of human genetic diseases. Mutations in the hydrocephalusinducing gene, hydin, in hy mice cause lethal communicating hydrocephalus with early onset [6,7] and the corresponding region within human chromosome 16 is associated with congenital hydrocephalus [8]. The first evidence for this came from localisation of the hydin transcript to ciliated ependyma in addition to spermocytes and oviduct and respiratory epithelia [6]. Further support for this idea comes from the recent completion of proteomic studies of eukaryotic cilia and flagella from Trypanosoma, Chlamydomonas and Tetrahymena [9,10,11], which enabled us to conduct a direct comparison of axonemal components from three diverse eukaryotes.

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