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.

Restoration of Physiological Expression of 5-HT6 Receptor into the Primary Cilia of Null Mutant Neurons Lengthens Both Primary Cilia and Dendrites

“…Trafficking of specific proteins into primary cilia is strictly regulated by the basal body and involves active transport along the central microtubule doublet that provides the cilia structure (Pazour and Bloodgood, 2008;Louvi and Grove, 2011;Stepanek and Pigino, 2016). Disruption of primary cilia function is linked with a variety of disorders termed ciliopathies, such as Bardet Biedl Syndrome, polycystic kidney disorder, polydactyly, hydrocephalus, obesity, disrupted neurogenesis, and cognitive disorders (Louvi and Grove, 2011;Lee and Gleeson, 2011;Valente et al, 2013;Gazea et al, 2016;Trulioff et al, 2017;Schmidt et al, 2017).…”

To beat, or not to beat, that is question! The spectrum of ciliopathies

“…These cilia have numerous roles in CNS development and function, including planar cell polarity, cell regulation, migration, differentiation, and signaling . Many ciliopathies have significant neurological features, most frequently mental retardation and CNS structural abnormalities, but recent associations with psychiatric disorders, including schizophrenia, have been suggested …”

“…Therefore, disorders of laterality may be a feature of motor and sensory ciliopathies . Laterality defects may be cardiac or vascular (with or without cardiovascular malformation), abdominal (ie, intestinal malrotation, liver, spleen or stomach malposition, asplenia or polysplenia), or pulmonary, and links between embryonic nodal cilia dysfunction and defects of left‐right development of the brain have been suggested …”

“…9,64 Many ciliopathies have significant neurological features, most frequently mental retardation and CNS structural abnormalities, 48,52,64 but recent associations with psychiatric disorders, including schizophrenia, have been suggested. 65,66 A classical neurodevelopmental ciliopathy, Joubert syndrome and related cerebellar disorders, is a genetically and phenotypically heterogeneous group of ciliopathies, involving at least eight different genes, and characterised by a specific form of cerebellar vermis hypoplasia and abnormal superior cerebellar peduncles. 2,15,64 The clinical manifestations include hypotonia, neurodevelopemental delay, ataxia, occulomotor and speech apraxia, and neonatal dysregulation of breathing patterns.…”

Neurodevelopmental disease mechanisms, primary cilia, and endosomes converge on the BLOC‐1 and BORC complexes

“…4B). A recent article reviews genes implicated in diverse neuropsychiatric disorders from a left-right patterning organ perspective (Trulioff et al, 2017).…”