Role of primary cilia in brain development and cancer

Abstract

SummaryThe primary cilium, a hair-like extension from a cell's surface, acts as a sensory organelle to receive signals that regulate cellular behavior and physiology. Like most mammalian cells, neural progenitors and neurons have primary cilia. Recent studies show that this tiny projection plays important roles in brain development and diseases. Ciliary mutant mice show defects in brain patterning, progenitor proliferation, and specification of adult neural stem cells. Primary cilia also have dual opposing functions in the development of brain tumors. Ciliary defects are associated with genetic syndromes that frequently have neurological symptoms. Understanding the multifaceted roles that primary cilia have in brain development will provide important insights into the mechanism of brain development and diseases.

Regulatory Factor X Transcription Factors Control Musashi1 Transcription in Mouse Neural Stem/Progenitor Cells

“…Because the Msi1 knockout mouse also shows hydrocephalus, there might be a relationship with the phenotype of the Rfx4-disrupted mouse. Although the functional role of Rfx transcription factors in NS/PCs has not been reported, primary cilia are required for the expansion and establishment of postnatal hippocampal progenitors [50][51][52]. Thus, it is speculated that Rfx transcription factors contribute to the regulation of NS/PCs regarding their maintenance or differentiation.…”

Biology of Cilia and Ciliopathies

“…SmoM2 leads to brain tumors only if primary cilia are present. However, Gli2∆N induces brain tumors only in the absence of cilia, since absence of cilia causes a disruption in Gli3, a repressor of Gli2∆N [174,176]. It appears that primary cilia are required both for the suppression and expression of oncogenisis.…”

“…It appears that primary cilia are required both for the suppression and expression of oncogenisis. Primary cilia suppress oncogenic mutations that act downstream of cilia, but allow expression of oncogenic mutations upstream of cilia [173,174,177]. Therefore, cilia can play opposite roles depending on the causal mutation of the cancer development [173,174].…”

“…Primary cilia appear to have dual opposing functions in development of different types of cancer, so that some refer to them as being an On/Off switch, regulating tumorigenesis [173,174]. One of the most important pathways related to ciliogenesis and cancer is the Hedgehog (Hh) pathway.…”

Le cil primaire, orchestrateur de la morphogenèse cérébrale

“…Mais, à l'époque, les cils étaient considérés comme des organites vestigiaux sans fonction particulière [1][2][3]. Ce n'est qu'avec l'analyse des lignées de souris dépourvues de cil et la description des syndromes humains dus à des dysfonctionnements ciliaires, que les fonctions de ce petit organite solitaire se sont révélées essentielles à de nombreux processus développementaux et, notamment, à la morphogenèse cérébrale [4,5]. Les ciliopathies sont des maladies génétiques dues à des dysfonctionnements du cil d'origine variable [6,67] ( §).…”