Abstract
Almost all brain cells contain primary cilia, antennae-like microtubule sensory organelles, on their surface, which play critical roles in brain functions. During neurodevelopmental stages, cilia are essential for brain formation and maturation. In the adult brain, cilia play vital roles as signaling hubs that receive and transduce various signals and regulate cell-to-cell communications. These distinct roles suggest that cilia functions, and probably structures, change throughout the human lifespan. To further understand the age-dependent changes in cilia roles, we identified and analyzed age-dependent patterns of expression of cilia’s structural and functional components across the human lifespan. We acquired cilia transcriptomic data for 16 brain regions from the BrainSpan Atlas and analyzed the age-dependent expression patterns using a linear regression model by calculating the regression coefficient. We found that 67% of cilia transcripts were differentially expressed genes with age (DEGAs) in at least one brain region. The age-dependent expression was region-specific, with the highest and lowest numbers of DEGAs expressed in the ventrolateral prefrontal cortex and hippocampus, respectively. The majority of cilia DEGAs displayed upregulation with age in most of the brain regions. The transcripts encoding cilia basal body components formed the majority of cilia DEGAs, and adjacent cerebral cortices exhibited large overlapping pairs of cilia DEGAs. Most remarkably, specific α/β-tubulin subunits (TUBA1A, TUBB2A, and TUBB2B) and SNAP-25 exhibited the highest rates of downregulation and upregulation, respectively, across age in almost all brain regions. α/β-tubulins and SNAP-25 expressions are known to be dysregulated in age-related neurodevelopmental and neurodegenerative disorders. Our results support a role for the high dynamics of cilia structural and functional components across the lifespan in the normal physiology of brain circuits. Furthermore, they suggest a crucial role for cilia signaling in the pathophysiological mechanisms of age-related psychiatric/neurological disorders.
Highlights
Primary cilia, antennae-like microtubule sensory organelles, protrude from the membranes of almost all cell types
Using linear regression to model the gene expression level as a function of the age, we found that out of 445 cilia transcripts, 299 (67% of cilia transcripts) were determined to follow linear regression in at least one brain region
The age-dependent expression was regionspecific, with the ventrolateral prefrontal cortex (VLPC) exhibiting the highest number of cilia DEGAs (132 cilia DEGAs) followed by posterior superior temporal cortex (PSTC) (123 cilia DEGAs), primary visual cortex (PVC) and orbital frontal cortex (OFC) (108 cilia DEGAs in each), and dorsolateral prefrontal cortex (DLPC) (99 cilia DEGAs), primary primary motor cortex (PMC) (91 cilia DEGAs), and posteroventral parietal cortex (PPC) (90 cilia DEGAs) (Figure 1b)
Summary
Antennae-like microtubule sensory organelles, protrude from the membranes of almost all cell types. Most primary cilia dysfunctions (called ciliopathies) are associated with neurological disorders, including cognitive deficits [11,12,13]. Cilia are continuously required for proper functions of the mature brain [5,14,15]. Besides their essential role in continuous neurogenesis in two regions of the adult brain (hippocampal dentate gyrus and ventricular–subventricular zone) [14], cilia act as signaling hubs to receive and transduce various signals and regulate cell–cell communications (see [15,16] for reviews)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
