Gene Expression at the Tripartite Synapse: Bridging the Gap Between Neurons and Astrocytes.

Astrocytes, a major class of glial cells, are an important element at the synapse where they engage in bidirectional crosstalk with neurons to regulate numerous aspects of neurotransmission, circuit function, and behavior. Mutations in synapse-related genes expressed in both neurons and astrocytes are central factors in a vast number of neurological disorders, making the proteins that they encode prominent targets for therapeutic intervention. Yet, while the roles of many of these synaptic proteins in neurons are well established, the functions of the same proteins in astrocytes are largely unknown. This gap in knowledge must be addressed to refine therapeutic approaches. In this chapter, we integrate multiomic meta-analysis and a comprehensive overview of current literature to show that astrocytes express an astounding number of genes that overlap with the neuronal and synaptic transcriptomes. Further, we highlight recent reports that characterize the expression patterns and potential novel roles of these genes in astrocytes in both physiological and pathological conditions, underscoring the importance of considering both cell types when investigating the function and regulation of synaptic proteins.

Pleiotropic function of the oca2 gene underlies the evolution of sleep loss and albinism in cavefish.

Adaptation to novel environments often involves the evolution of multiple morphological, physiological, and behavioral traits. One striking example of multi-trait evolution is the suite of traits that has evolved repeatedly in cave animals, including regression of eyes, loss of pigmentation, and enhancement of non-visual sensory systems.1,2 The Mexican tetra, Astyanax mexicanus, consists of fish that inhabit at least 30 caves in Mexico and ancestral-like surface fish that inhabit the rivers of Mexico and southern Texas.3 Cave A. mexicanus are interfertile with surface fish and have evolved a number of traits, including reduced pigmentation, eye loss, and alterations to behavior.4-6 To define relationships between different cave-evolved traits, we phenotyped 208 surface-cave F2 hybrid fish for numerous morphological and behavioral traits. We found differences in sleep between pigmented and albino hybrid fish, raising the possibility that these traits share a genetic basis. In cavefish and other species, mutations in oculocutaneous albinism 2 (oca2) cause albinism.7-12 Surface fish with mutations in oca2 displayed both albinism and reduced sleep. Further, this mutation in oca2 fails to complement sleep loss when surface fish harboring this engineered mutation are crossed to independently evolved populations of albino cavefish with naturally occurring mutations in oca2. Analysis of the oca2 locus in wild-caught cave and surface fish suggests that oca2 is under positive selection in 3 cave populations. Taken together, these findings identify oca2 as a novel regulator of sleep and suggest that a pleiotropic function of oca2 underlies the adaptive evolution of albinism and sleep loss.