Species differences in the expression of Ahi1, a protein implicated in the neurodevelopmental disorder Joubert syndrome, with preferential accumulation to stigmoid bodies

Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
The Journal of Comparative Neurology (Impact Factor: 3.23). 11/2008; 511(2):238-56. DOI: 10.1002/cne.21824
Source: PubMed


Joubert syndrome (JBTS) is an autosomal recessive disorder characterized by cerebellum and brainstem malformations. Individuals with JBTS have abnormal breathing and eye movements, ataxia, hypotonia, and cognitive difficulty, and they display mirror movements. Mutations in the Abelson-helper integration site-1 gene (AHI1) cause JBTS in humans, suggesting that AHI1 is required for hindbrain development; however AHI1 may also be required for neuronal function. Support for this idea comes from studies demonstrating that the AHI1 locus is associated with schizophrenia. To gain further insight into the function of AHI1 in both the developing and mature central nervous system, we determined the spatial and temporal expression patterns of the gene products of AHI1 orthologs throughout development, in human, mouse, and zebrafish. Murine Ahi1 was distributed throughout the cytoplasm, dendrites, and axons of neurons, but was absent in glial cells. Ahi1 expression in the mouse brain was observed as early as embryonic day 10.5 and persisted into adulthood, with peak expression during the first postnatal week. Murine Ahi1 was observed in neurons of the hindbrain, midbrain, and ventral forebrain. Generally, the AHI1/Ahi1/ahi1 orthologs had a conserved distribution pattern in human, mouse, and zebrafish, but mouse Ahi1 was not present in the developing and mature cerebellum. Ahi1 was also observed consistently in the stigmoid body, a poorly characterized cytoplasmic organelle found in neurons. Overall, these results suggest roles for AHI1 in neurodevelopmental processes that underlie most of the neuroanatomical defects in JBTS, and perhaps in neuronal functions that contribute to schizophrenia.

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Article: Species differences in the expression of Ahi1, a protein implicated in the neurodevelopmental disorder Joubert syndrome, with preferential accumulation to stigmoid bodies

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    • "There has been no previous documentation of AHI1 spatial expression during development in human tissue. Previous characterisation has been limited to hybridisation to RNA northern blot showing expression in fetal brain, kidney, liver and lung [13], [14] and Western blotting, demonstrating Ahi1 protein expression in fetal cerebellum and spinal cord [50]. "
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    • "Both mouse and human Ahi-1/AHI-1 are highly expressed in brain and testis and have lower expression in liver, lung, thymus, kidney and pancreas [16, 56]. We and others have recently demonstrated that Ahi-1 transcripts are expressed at all stages of mouse embryo development, with increasing expression just prior to birth, suggesting that Ahi-1 expression is developmentally regulated [16, 21, 56]. Mouse Ahi-1 mRNA in the cerebellum has its highest expression at E18 and P5, whereas expression in the cerebral cortex appears maximally at E16 and E18 [21]. "
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