Journal
BIOLOGY OPEN
Volume 10, Issue 6, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.056457
Keywords
FAT1; Cadherin; Cerebellum; Granule cells; Autism; Neural precursor cells
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Funding
- Hussman Foundation [15007, 18005, 15003, 18004]
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Genetic studies have linked FAT1 with autism spectrum disorder, and it is expressed in postnatal mouse brains with a unique localization pattern. The decreased expression of FAT1 in neural precursor cells from individuals with ASD suggests a potential role in the disease etiology, particularly in cerebellum function, which is a vulnerable brain region in ASD.
Genetic studies have linked FAT1 (FATatypical cadherin 1) with autism spectrum disorder (ASD); however, the role that FAT1 plays in ASD remains unknown. In mice, the function of Fat1 has been primarily implicated in embryonic nervous system development with less known about its role in postnatal development. We show for the first time that FAT1 protein is expressed in mouse postnatal brains and is enriched in the cerebellum, where it localizes to granule neurons and Golgi cells in the granule layer, as well as inhibitory neurons in the molecular layer. Furthermore, subcellular characterization revealed FAT1 localization in neurites and soma of granule neurons, as well as being present in the synaptic plasma membrane and postsynaptic densities. Interestingly, FAT1 expression was decreased in induced pluripotent stem cell (iPSC)-derived neural precursor cells (NPCs) from individuals with ASD. These findings suggest a novel role for FAT1 in postnatal development and may be particularly important for cerebellum function. As the cerebellum is one of the vulnerable brain regions in ASD, our study warrants further investigation of FAT1 in the disease etiology.
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