The primary cilium: a signalling centre during vertebrate development

Abstract

The primary cilium has recently stepped into the spotlight, as a flood of data demonstrate that this organelle has crucial roles in vertebrate development and human genetic diseases. Cilia are required for the response to developmental signals, and evidence is accumulating that the primary cilium is specialized for Hedgehog (Hh) signal transduction. Formation of cilia, in turn, is regulated by other signaling pathways, possibly including the planar cell polarity pathway. The cilium therefore represents a nexus for signaling pathways during development. The connections between cilia and developmental signaling have begun to clarify the basis of human diseases associated with ciliary dysfunction.

Tectonic gene mutations in patients with Joubert syndrome

“…8 In 2006, a new protein, tectonic, was described to be involved in the Hedgehog-mediated patterning of the neural tube. 9 The encoding gene TCTN1 was found to be a member of a novel gene family with two other members involved, TCTN2 and TCTN3 that share 49% and 58% similarity, respectively.…”

“…5,10 Hedgehog signaling is involved in the patterning of the embryo and defects of the pathway can lead to symptoms like polydactyly, skeletal and central nervous system anomalies. 8 Subsequently, sequence variants in all three genes have been reported to cause disorders of the ciliopathy spectrum. So far, sequence variants in TCTN3 have been described in six fetuses with OFD IV and MKS and two siblings with Joubert syndrome.…”

Ce que les planaires nous apprennent sur les cils, les centrioles et les centrosomes

“…Chez l'humain, des mutations qui affectent l'assemblage des cils sont à l'origine d'une classe de pathologies appelées ciliopathies. Celles-ci peuvent consister en des anomalies du développement comme l'hydrocéphalie ou la polykystose rénale, ou encore s'accompagner d'infections respiratoires chroniques et de problèmes de fertilité [1]. Les cils sont assemblés à partir des centrioles, des organites cylindriques constitués d'une grande diversité de protéines dont beaucoup n'ont pas encore été caractérisées.…”

“…Les cellules souches du gyrus denté et de la zone sous-ventriculaire Ces dernières décennies ont été marquées par la découverte de cellules souches (CS) dans certaines régions du cerveau adulte : le gyrus denté et la zone sous-ventriculaire (ZSV). Ces cellules donnent naissance, tout au long de la vie, à des neurones aux fonctions particulières : les neurones issus des cellules souches du gyrus denté s'intègrent dans les circuits propres à cette structure [1] et participent, directement ou indirectement, à la ségrégation spatiale des réseaux neuronaux [2]. Les cellules souches de la ZSV assurent le renouvellement des interneurones et neurones périglomérulaires du bulbe olfactif dont…”

Targeting the CB2 cannabinoid receptor in osteoporosis

“…A diagram of the general intracellular process that accompanies hedgehog signaling is shown in Figure 1. It should be noted that the brief schema described here is specific for vertebrate-derived cells as evolution from invertebrates was accompanied by modifications that tether the proximal stage of hedgehog signal processing to the subcellular organelle referred to as the primary cilia [27,28]. The integration of hedgehog signaling into the primary cilia provides vertebrate cells with unique opportunities to regulate the signaling process, but the linkage also has some important implications for our understanding of hedgehog action in human tumors, as will be discussed later.…”