Firmly established as a model organism for embryonic developmental studies, zebrafish
is now emerging as an effective system to elucidate the fundamental aspects of several
human diseases. Despite the significant evolutionary distance, gene functions and
pathways are often highly conserved between zebrafish and humans. Previous work has
identified nonsense mutations, associated with hearing deficiency, in the small muscle
protein, X-linked (SMPX) gene and a loss-of-function mechanism underlying this form of
impairment has been proposed. SMPX encodes a cytoskeleton-associated protein that
has been suggested being responsive to mechanical stress. The presence of Smpx in hair
cells of the murine cochlea reinforces the thesis of its importance in ear functioning.
In this study we first provided an overview of the expression of smpx during zebrafish
embryonic development. We showed that from the 4-somite stage, zebrafish smpx was
first expressed in the ciliated organ Kupffer\u2019s vesicle (KV), responsible for the left-right
organs asymmetry, and then, as in mammals, expressed in the heart and in the inner
ear, among other territories. Knock-down of smpx in zebrafish embryos resulted in the
reduced number of cilia in KV and, consequently, the left-right patterning of internal
organs resulted compromised, mimicking human heterotaxy, a disorder of laterality.
Moreover, smpx knock-down resulted in the marked decrease of the number of cilia in
the ear macular regions, providing a possible explanation for the hearing loss in SMPXmutated
patients.
In conclusion, this study contributes to the comprehension of the link between SMPX and
human hearing loss, delivers a novel heterotaxy-candidate gene, and finally provides a
robust animal tool for the future elucidation of the mechanisms behind both
deafness/hearing loss and heterotaxy