| Résumé: | <p>Cilia are cellular organelles involved in processing components of the hedgehog (hh) signalling pathway and determining left-right (L-R) axis formation in the embryo. An embryonic lethal mouse mutant, called <em>gasping 6</em> (<em>gpg6</em>), was identified that demonstrated morphological and molecular defects associated with L-R development and hh signalling. <em>gpg6</em> mutant embryos also demonstrate abnormally short cilia, which was hypothesised to be the primary morphological defect in <em>gpg6</em> mutants.</p> <p>The underlying genetic lesion in <em>gpg6</em> is a mutation in the DNA repair gene <em>Atmin</em>. The base pair change results in an amino acid substitution in a critical residue in the third zinc finger of <em>Atmin</em>. The consequence of this change is the failure to activate transcriptional targets of <em>Atmin</em>. This raised the possibility that previously unidentified <em>Atmin</em> target genes are important for ciliogenesis. Consistent with this hypothesis, <em>Dynein light chain-LC8</em> (<em>Dynll1</em>) is downregulated in <em>gpg6</em> mutants. LC8 (a homolog of mouse <em>Dynll1</em>) is required, in the single cell eukaryotic organism <em>Chlamydomonas</em>, for retrograde intraflagellar transport (IFT), a process crucial for ciliogenesis.</p> <p>These data led to the following hypothesis: <em>Atmin</em> activates expression of <em>Dynll1</em>, which functions in retrograde IFT to enable normal ciliogenesis. Knockdown of <em>Atmin</em> in a ciliated kidney cell line resulted in abnormally short cilia. Thus, <em>Atmin</em> functions in ciliogenesis. Investigation of <em>gpg6</em> has therefore identified a novel role for <em>Atmin</em> in ciliogenesis and has added to the growing knowledge of genes that control cilia formation and embryonic development.</p>
|
|---|