Development and distribution of neuronal cilia in mouse neocortex

Abstract

Neuronal primary cilia are not generally recognized, but they are considered to extend from most, if not all, neurons in the neocortex. However, when and how cilia develop in neurons are not known. This study used immunohistochemistry for adenylyl cyclase III (ACIII), a marker of primary cilia, and electron microscopic analysis to describe the development and maturation of cilia in mouse neocortical neurons. Our results indicate that ciliogenesis is initiated in late fetal stages after neuroblast migration, when the mother centriole docks with the plasma membrane, becomes a basal body, and grows a cilia bud that we call a procilium. This procilium consists of a membranous protrusion extending from the basal body but lacking axonemal structure and remains undifferentiated until development of the axoneme and cilia elongation starts at about postnatal day 4. Neuronal cilia elongation and final cilia length depend on layer position, and the process extends for a long time, lasting 8–12 weeks. We show that, in addition to pyramidal neurons, inhibitory interneurons also grow cilia of comparable length, suggesting that cilia are indeed present in all neocortical neuron subtypes. Furthermore, the study of mice with defective ciliogenesis suggested that failed elongation of cilia is not essential for proper neuronal migration and laminar organization or establishment of neuronal polarity. Thus, the function of this organelle in neocortical neurons remains elusive.

Critical roles of αII spectrin in brain development and epileptic encephalopathy

“…Neuronal primary cilia are recognized as key integrators of extracellular ligand-based signaling required for appropriate cellular polarity development, and in cortical neurons the primary cilium invariably extends from the base of the apical dendrite (21). Therefore, we used adenylyl cyclase III (ACIII), a wellestablished marker of neuronal cilia, to ask whether this highly polarized organelle is also disrupted (21).…”

“…Therefore, we used adenylyl cyclase III (ACIII), a wellestablished marker of neuronal cilia, to ask whether this highly polarized organelle is also disrupted (21). We noted that in contrast to the disappearance of ankyrin-G and βIV spectrin clustering, ACIII immunoreactivity was well preserved, but its distribution was mislocalized to the basal aspect of cortical neurons after Sptan1 deletion (Figure 4, C-E).…”

Neonatal seizures induced by pentylenetetrazol or kainic acid disrupt primary cilia growth on developing mouse cortical neurons

“…Extension of procilia is a key step during neuronal ciliogenesis (Arellano et al, 2012). Thus, if seizures occurred around or shortly after birth when procilia are maturing, then it is possible that disruption of ciliogenesis by ELS could be a subtle but significant factor underlying many of the widespread effects that seizures have on brain structure and connectivity.…”

“…Many cell types found throughout the murine neocortex synthesize primary cilia, a process that begins at birth. During the first postnatal week, an immature procilium will differentiate into a more organized cilium which continues to elongate over the first 90 days of life (Arellano et al, 2012).…”

Neuron's little helper: The role of primary cilia in neurogenesis

“…42 What could be the function of primary cilia here? One possibility is that this cilia growth is just a preparation for their signaling roles in adult neurons.…”