Primary Cilia as a Possible Link between Left-Right Asymmetry and Neurodevelopmental Diseases

Abstract

Cilia have multiple functions in the development of the entire organism, and participate in the development and functioning of the central nervous system. In the last decade, studies have shown that they are implicated in the development of the visceral left-right asymmetry in different vertebrates. At the same time, some neuropsychiatric disorders, such as schizophrenia, autism, bipolar disorder, and dyslexia, are known to be associated with lateralization failure. In this review, we consider possible links in the mechanisms of determination of visceral asymmetry and brain lateralization, through cilia. We review the functions of seven genes associated with both cilia, and with neurodevelopmental diseases, keeping in mind their possible role in the establishment of the left-right brain asymmetry.

Keywords: DCDC2; Disc1; Dyx1c1; PCM-1; abelson helper integrator 1; centrosome; hamartin; left-right asymmetry; pericentrin; schizophrenia.

Figure 1

Ciliary proteins localization in a cilium. Most of the proteins are localized in the basal body, AHI1 is localized in the transition zone, and two of the proteins are localized in the axoneme.

Figure 2

A scheme of known relations between proteins under review. Continuous line between proteins means direct interactions. Dashed line means that a pair of proteins has common binding partners, their names are given near the dashed line.

Figure 3

A scheme of suggested associations between the ciliary proteins and neurodevelopmental diseases. Striped sectors indicate that the protein is associated with at least two diseases. Note different location in the cilia or protein complexes of those ciliary proteins related to different diseases.