Investigating embryonic expression patterns and evolution of AHI1 and CEP290 genes, implicated in Joubert syndrome

PLoS One. 2012;7(9):e44975. doi: 10.1371/journal.pone.0044975. Epub 2012 Sep 24.

Abstract

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 MRC-Wellcome 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Brain / embryology
  • Brain / metabolism
  • Cell Cycle Proteins
  • Cell Line
  • Centrosome / metabolism
  • Cerebellar Diseases / embryology
  • Cerebellar Diseases / genetics*
  • Cerebellum / abnormalities
  • Conserved Sequence
  • Cytoskeletal Proteins
  • Evolution, Molecular*
  • Eye Abnormalities / embryology
  • Eye Abnormalities / genetics*
  • Gene Expression Regulation, Developmental*
  • Genomics
  • Humans
  • Kidney / embryology
  • Kidney / metabolism
  • Kidney Diseases, Cystic / embryology
  • Kidney Diseases, Cystic / genetics*
  • Mice
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Organ Specificity
  • Protein Transport
  • Retina / abnormalities
  • Retina / embryology

Substances

  • AHI1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Antigens, Neoplasm
  • Cell Cycle Proteins
  • Cep290 protein, human
  • Cytoskeletal Proteins
  • Neoplasm Proteins

Supplementary concepts

  • Agenesis of Cerebellar Vermis