The unexpected connection between cilia and signaling is one of the most exciting developments in cell biology in the past decade. In particular, the Hedgehog (Hh) signaling pathway relies on the primary cilium to regulate tissue patterning and homeostasis in vertebrates. A central question is how ciliary localization and trafficking of Hh pathway components lead to pathway activation and regulation. In this review, we discuss recent studies that reveal the roles of ciliary regulators, components and structures in controlling the movement and signaling of Hh players. These findings significantly increase our mechanistic understanding of how the primary cilium facilitates Hh signal transduction and form the basis for further investigations to define the function of cilia in other signaling processes.
Background: Motile cilia on the inner lining of the oviductal epithelium play a central role in ovum transport toward the uterus and subsequent fertilization by sperm. While the basic ultrastructure of 912 motile cilia (nine peripheral microtubule doublets surrounding a central pair) has been characterized, many important steps of ciliogenesis remain poorly understood. Results: Our previous studies on mammalian Fused (Fu) (Stk36), a putative serine-threonine kinase, reveal a critical function of Fu in central pair construction and cilia orientation of motile cilia that line the tracheal and ependymal epithelia. These findings identify a novel regulatory component for these processes. In this study, we show that Fu is expressed in the multi-ciliated oviductal epithelium in several vertebrates, suggesting a conserved function of Fu in the oviduct. In support of this, analysis of Fu-deficient mouse oviducts uncovers a similar role of Fu in central pair construction and cilia orientation. We also demonstrate that Fu localizes to motile cilia and physically associates with kinesin Kif27 located at the cilium base and known central pair components Spag16 and Pcdp1. Conclusions: Our results delineate a novel pathway for central pair apparatus assembly and add important insight to the biogenesis and function of oviductal motile cilia. Developmental Dynamics 242:1307-1319, 2013. V C 2013 Wiley Periodicals, Inc.Key words: Fu (Stk36); motile cilia; oviduct; Kif27; central pair; primary ciliary dyskinesia
Key findings:Fu is required for central pair construction and cilia orientation in the mammalian oviduct. Fu is a ciliary protein that is localized along the entire length of motile cilia. Fu physically associates with kinesin Kif27, located at the cilium base, and two central pair proteins, Spag16 and Pcdp1. Our findings affirm a central role of Fu in motile ciliogenesis in multi-ciliated tissues and provide a new pathway for understanding central pair assembly.
A comprehensive understanding of coral reproduction and development is needed because corals are threatened in many ways by human activity. Major threats include the loss of their photosynthetic symbionts (Symbiodinium) caused by rising temperatures (bleaching), reduced ability to calcify caused by ocean acidification, increased storm severity associated with global climate change and an increase in predators caused by runoff from human agricultural activity. In spite of these threats, detailed descriptions of embryonic development are not available for many coral species. The current consensus is that there are two major groups of stony corals, the "complex" and the "robust". In this paper we describe the embryonic development of four "complex" species, Pseudosiderastrea tayamai, Galaxea fascicularis, Montipora hispida, and Pavona Decussata, and seven "robust" species, Oulastrea crispata, Platygyra contorta, Favites abdita, Echinophyllia aspera, Goniastrea favulus, Dipsastraea speciosa (previously Favia speciosa), and Phymastrea valenciennesi (previously Montastrea valenciennesi). Data from both histologically sectioned embryos and whole mounts are presented. One apparent difference between these two major groups is that before gastrulation the cells of the complex corals thus far described (mainly Acropora species) spread and flatten to produce the so-called prawn chip, which lacks a blastocoel. Our present broad survey of robust and complex corals reveals that prawn chip formation is not a synapomorphy of complex corals, as Pavona Decussata does not form a prawn chip and has a well-developed blastocoel. Although prawn chip formation cannot be used to separate the two clades, none of the robust corals which we surveyed has such a stage. Many robust coral embryos pass through two periods of invagination, separated by a return to a spherical shape. However, only the second of these periods is associated with endoderm formation. We have therefore termed the first invagination a pseudo-blastopore.
This study was conducted at a high-latitude location (32°N; Kochi, Japan), where annual seawater temperatures show large fluctuations due to the meandering of the Kuroshio Current, providing a unique opportunity to examine the influence of temperature on coral reproduction. Annual spawning of individual colonies of four reef coral species-two Acropora species (Acropora hyacinthus and A. japonica) and two faviid species (Favites pentagona and Platygyra contorta)-was monitored in situ for 4 years in 2006-2009. The spawning of the four species always occurred around the last quarter moon in the local summer, July or August, irrespective of high annual variations in seawater temperatures (from 23.7 to 29.5 °C) and weather during the spawning period. However, the exact timing of spawning during the spawning period varied among the years and was correlated with the cumulative seawater temperature during the late period of gametogenesis (0-3 months before spawning). When seawater temperatures were higher, spawning occurred in the earlier spawning month (July) and vice versa, except in A. hyacinthus, which always spawned in July. In the case of the two Acropora species, higher (lower) temperatures led to spawning earlier (later) in the lunar cycle. Seawater temperature may have an influence on gametogenesis, causing the shift in spawning timing.
Control of Gli function by Suppressor of Fused (Sufu), a major negative regulator, is a key step in mammalian Hedgehog (Hh) signaling, but how this is achieved in the nucleus is unknown. We found that Hh signaling results in reduced Sufu protein levels and Sufu dissociation from Gli proteins in the nucleus, highlighting critical functions of Sufu in the nucleus. Through a proteomic approach, we identified several Sufu-interacting proteins, including p66b (a member of the NuRD [nucleosome remodeling and histone deacetylase] repressor complex) and Mycbp (a Myc-binding protein). p66b negatively and Mycbp positively regulate Hh signaling in cell-based assays and zebrafish. They function downstream from the membrane receptors, Patched and Smoothened, and the primary cilium. Sufu, p66b, Mycbp, and Gli are also detected on the promoters of Hh targets in a dynamic manner. Our results support a new model of Hh signaling in the nucleus. Sufu recruits p66b to block Gli-mediated Hh target gene expression. Meanwhile, Mycbp forms a complex with Gli and Sufu without Hh stimulation but remains inactive. Hh pathway activation leads to dissociation of Sufu/p66b from Gli, enabling Mycbp to promote Gli protein activity and Hh target gene expression. These studies provide novel insight into how Sufu controls Hh signaling in the nucleus.
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