Joubert syndrome and related diseases (JSRD) are developmental cerebello-oculo-renal syndromes with phenotypes
including cerebellar hypoplasia, retinal dystrophy and nephronophthisis (a cystic kidney disease). We have utilised the MRCWellcome
Trust Human Developmental Biology Resource (HDBR), to perform in-situ hybridisation studies on embryonic
tissues, revealing an early onset neuronal, retinal and renal expression pattern for AHI1. An almost identical pattern of
expression is seen with CEP290 in human embryonic and fetal tissue. A novel finding is that both AHI1 and CEP290
demonstrate strong expression within the developing choroid plexus, a ciliated structure important for central nervous
system development. To test if AHI1 and CEP290 may have co-evolved, we carried out a genomic survey of a large group of
organisms across eukaryotic evolution. We found that, in animals, ahi1 and cep290 are almost always found together;
however in other organisms either one may be found independent of the other. Finally, we tested in murine epithelial cells
if Ahi1 was required for recruitment of Cep290 to the centrosome. We found no obvious differences in Cep290 localisation
in the presence or absence of Ahi1, suggesting that, while Ahi1 and Cep290 may function together in the whole organism,
they are not interdependent for localisation within a single cell. Taken together these data support a role for AHI1 and
CEP290 in multiple organs throughout development and we suggest that this accounts for the wide phenotypic spectrum
of AHI1 and CEP290 mutations in man.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)