The Role Of Ahi1 In Zebrafish Neural Development

The Ahi1(Abelson helper integration site-1)gene encodes an intracellular scaffold protein with multiple domains,which can mediate protein-protein interactions in the cytoplasm.Ahi1 was the first mutant gene identified in Joubert Syndrome and the ahi1 mutations can lead to typical Joubert Syndrome.Joubert Syndrome is a rare autosomal recessive inherited diseases with a characterized imaging feature of “Molar tooth sign” caused by the defects in cerebellar vermis and brain stem and the failing of corticospinal fiber decussation.Recent research also suggests that Ahi1 is closely connected with autism,schizophrenia,bipolar disorder and other neurodevelopmental disorders.So Ahi1 may play an important role in neural development.There is evidence suggests that Ahi1 participates in beta-catenin aggregation in cytoplasm and transportation into the nucleus.The classical Wnt/beta-catenin signaling pathway is critical for the proliferation,differentiation and polarity of neural cells.Ahi1 has been indicated to regulate cerebellar development through Wnt signaling pathway,however,the underlying molecular and cellular mechanisms still remain obscure.Compared with human Ahi1 protein,the zebrafish version is more conservative than that of mice.In the present study,we used zebrafish as a model organism,using microinjection,molecular cloning,in situ hybridization and immunofluorescent experimental approaches to study the role of Ahi1 in axon outgrowth and guidance in vivo.We also studied the components of classical Wnt signaling pathways,such as: Wnt1,Apc1,Gsk-3beta in cerebellar development and their relationship with Ahi1.We found that Ahi1 not only have certain effect for some of the axons growth and guidance in the peripheral nervous system,also has a key role in the development of the cerebellum in the central nervous system.The outer peripheral nervous including optic nerve,trigeminal,face,tongue pharynx,vagus nerve,and motor nerve,Ahi1 plays significant role in axons growth and guidance;In the central nervous system,Ahi1 has function to cerebellum early and late GABA and glutamic acid nerve cells development of growth,proliferation and differentiation,the main of classic Wnt signaling pathways relevant genes also have similar phenotypic in the cerebellum to the ahi1 knocked down,thus further suggested that Ahi1 and classic Wnt signaling pathways may have relevance in the development of the cerebellum.This study found that Ahi1 biological functional diversity,not only in a variety of neural axon growth and play an important role in guiding,also play an important role in the development of the cerebellum,the findings help to understand the Ahi1 associated with a variety of nerve of mental illness,for understanding the pathogenic mechanisms of Ahi1 also has important significance.