Progressive myoclonic epilepsy-associated gene Kctd7 regulates retinal neurovascular patterning and function. (October 2019)

• Record Type: Journal Article
• Authors: Alevy, Jonathan; Burger, Courtney A.; Albrecht, Nicholas E.; Jiang, Danye; Samuel, Melanie A.
• Is Part Of: Neurochemistry international. Volume 129(2019)
• Publication Date: 2019-10
• Subjects: Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2019.104486
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: Neuron function relies on and instructs the development and precise organization of neurovascular units that in turn support circuit activity. However, our understanding of the molecular cues that regulate this relationship remains sparse. Using a high-throughput screening pipeline, we recently identified several new regulators of vascular patterning. Among these was the potassium channel tetramerization domain-containing protein 7 (KCTD7). Mutations in KCTD7 are associated with progressive myoclonic epilepsy, but how KCTD7 regulates neural development and function remains poorly understood. To begin to identify such mechanisms, we focus on mouse retina, a tractable part of the central nervous system that contains precisely ordered neuron subtypes supported by a trilaminar vascular network. We find that deletion of Kctd7 induces defective patterning of the adult retina vascular network, resulting in increased branching, vessel length, and lacunarity. These alterations reflect early and specific defects in vessel development, as emergence of the superficial and deep vascular layers were delayed. These defects are likely due to a role for Kctd7 in inner retina neurons. Kctd7 is absent from vessels but present in neurons in the inner retina, and its deletion resulted in a corresponding increase in the number of bipolar cells in development and increased vessel branching in adults. These alterations were accompanied by retinal function deficits. Together, these data suggest that neuronal Kctd7 drives growth and patterning of the vasculature and that neurovascular interactions may participate in the pathogenesis of KCTD7-related human diseases. Graphical abstract: Image 1 Highlights: Kctd7 is required for normal retinal vascular organization and retinal function in adults. Deletion of Kctd7 disrupts the emergence of the superficial and deep vessel layers. Kctd7 may impact vascular patterning through influencing neurons as it is expressed in and regulates bipolar cells. Kctd7 driven neurovascular interactions may participate in the pathogenesis of KCTD7-related human diseases.