Intraflagellar Transport Is Required in Drosophila to Differentiate Sensory Cilia but Not Sperm

Han, Young-Goo; Kwok, Benjamin H.; Kernan, Maurice J.

doi:10.1016/j.cub.2003.08.034

Cited by 210 publications

(236 citation statements)

References 56 publications

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“…However, some differences in these processes have also been reported. For example, it has been demonstrated in Drosophila that IFT is required to differentiate sensory cilia, but not spermatozoa (13). Further study will be necessary to determine whether the functions of the BBS proteins are limited to a subset of cilia.…”

Section: Discussionmentioning

confidence: 99%

Bardet–Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly

Mykytyn

Mullins²,

Andrews³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

308

303

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The functions of the proteins encoded by the Bardet-Biedl syndrome (BBS) genes are unknown. Mutations in these genes lead to the pleiotropic human disorder BBS, which is characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Secondary features include diabetes mellitus and hypertension. Recently, it has been suggested that the BBS phenotypes are the result of a lack of cilia formation or function. In this study, we show that mice lacking the Bbs4 protein have major components of the human phenotype, including obesity and retinal degeneration. We show that Bbs4-null mice develop both motile and primary cilia, demonstrating that Bbs4 is not required for global cilia formation. Interestingly, male Bbs4-null mice do not form spermatozoa flagella, and BBS4 retinopathy involves apoptotic death of photoreceptors, the primary ciliated cells of the retina. These mutation data demonstrate a connection between the function of a BBS protein and cilia. To further evaluate an association between cilia and BBS, we performed homology comparisons of BBS proteins in model organisms and find that BBS proteins are specifically conserved in ciliated organisms.B ardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder with linkage to eight loci. Six BBS genes (BBS1, BBS2, BBS4, BBS6, BBS7, and BBS8) have been identified (1-7). With the exception of BBS6, which has similarity to type II chaperonins (8), BBS proteins do not show extensive homology with proteins of known function. BBS4 and BBS8 contain tetratricopeptide repeat domains, and a region of BBS8 shows similarity to the prokaryotic pilF domain. Based on the observations that BBS8 localizes to the basal body of ciliated cells and expression of the Caenorhabditis elegans orthologues of several BBS proteins are limited to ciliated cells, it has been hypothesized that BBS is the result of a defect in cilia assembly or function (7). We previously used positional cloning to identify the human BBS4 gene (3). To help elucidate the function of the BBS proteins, we have now targeted the Bbs4 gene in mice. Bbs4 Ϫ/Ϫ mice recapitulate aspects of the human phenotype: they become obese, fail to reproduce, and display retinal degeneration. We show the presence of both motile and primary cilia in these mice, demonstrating that Bbs4 deficiency does not prevent global ciliogenesis. Interestingly, male knockout mice have a complete lack of flagella, demonstrating that the Bbs4 protein is necessary for flagella formation during spermatogenesis. Furthermore, Bbs4-null mice undergo retinal degeneration due principally to photoreceptor cell loss associated with outer segment attenuation, suggesting a role for BBS proteins in maintenance of sensory cilia. These data demonstrate a role for BBS proteins in facets of cilia function. Materials and MethodsConstruction of the Bbs4 Gene Targeting Vector. BLAST analysis of the Celera mouse fragment database with the human BBS4 cDNA sequence identified sequences corresponding to...

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Section: Discussionmentioning

confidence: 99%

Bardet–Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly

Mykytyn

Mullins²,

Andrews³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

308

303

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“…Sperm lengths of millimeters are common within this group, with the 1.8 mm sperm of D. melanogaster being fairly typical. This marked expansion in sperm length reflects an unusual aspect of spermatogenesis in these organisms: in contrast to other species in which an intraflagellar transport system is used for growth of the sperm flagellum (Scholey, 2006), Drosophila sperm axonemes are assembled in syncytial cysts by a mechanism that does not require, and is not limited by, this system (Han et al, 2003;Sarpal et al, 2003). This unusual sperm axoneme development and the resulting expansion of sperm tail length have led to distinctive features of spermatogenesis not found in other species.…”

mentioning

confidence: 84%

yuri gagarinis required for actin, tubulin and basal body functions inDrosophilaspermatogenesis

Texada

Simonette

Johnson

et al. 2008

Journal of Cell Science

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A unique feature of the genus Drosophila is the formation of unusually long sperm tails. Sperm lengths of millimeters are common within this group, with the 1.8 mm sperm of D. melanogaster being fairly typical. This marked expansion in sperm length reflects an unusual aspect of spermatogenesis in these organisms: in contrast to other species in which an intraflagellar transport system is used for growth of the sperm flagellum (Scholey, 2006), Drosophila sperm axonemes are assembled in syncytial cysts by a mechanism that does not require, and is not limited by, this system (Han et al., 2003;Sarpal et al., 2003). This unusual sperm axoneme development and the resulting expansion of sperm tail length have led to distinctive features of spermatogenesis not found in other species. In D. bifurca, a special 'sperm roller' has evolved to package its 6-centimeter-long gametes (Joly et al., 2003). In D. melanogaster, a highly evolved individualization process that generates 64 individual sperm from an elongate cyst containing 64 syncytial spermatids has been identified and studied (Noguchi and Miller, 2003;Tokuyasu et al., 1972a). The distinctive molecular mechanisms needed for this process include a motile filamentous actin system (the investment, or actin, cones) that traverses the entire length of the sperm tails, removing excess cytoplasm and investing each sperm in its own plasma membrane. A specialized microtubulerich structure (the dense complex) is also associated with the sperm nuclei and functions to position the basal body and also possibly to strengthen the nuclei as they undergo extreme condensation (A. D. Tates, Cytodifferentiation during spermatogenesis in Drosophila melanogaster, PhD thesis, Rijksuniversiteit Leiden, The Netherlands, 1971) (Tokuyasu, 1974).We have identified a locus, yuri gagarin (yuri), that we show here has multiple roles in the generation of elongate individualized sperm. The gene is only highly conserved in the genus Drosophila, suggesting specialized roles in these organisms. Interestingly, yuri was initially identified through its function in another specialized organ system of insects and arthropods: the chordotonal organs. These are complex mechanosensory structures with roles in proprioception and graviperception. The first mutation at the locus, yuri c263 , was identified in a screen for mutants affecting gravitaxis. Altered gravitaxis was shown to result from perturbed expression of yuri in subsets of chordotonal neurons (Armstrong et al., 2006). The molecular functions of the locus identified here suggest that yuri mediates specialized actin-and microtubule-related activities in Drosophila tissues. ResultsThe yuri locus in D. melanogaster and other Drosophilids In addition to the cDNA (GH14032) encoding a ~30 kDa protein that we used previously (Armstrong et al., 2006), we identified 11 further yuri ESTs/cDNAs from adult testis, ovary, S2 cells and embryos through FlyBase. Sequencing of these new cDNAs established that three major transcript classes are generated from yuri (Fig...

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“…A thin process that stains for the protein cofilin and was identified as the neuronal dendrite [89] also always lies along the upper surface of the trichogen extension and, thus, may also determine its initial orientation. However, mutants that cannot form neuronal outer segments [8,25,41] still have normal bristle orientation and morphology, so either this process is not required to orient the bristle, or it extends from a non-neuronal cell-possibly the thecogen.…”

Section: Early Development Of Sense Organsmentioning

confidence: 99%

Mechanotransduction and auditory transduction in Drosophila

Kernan

2007

Pflugers Arch - Eur J Physiol

Self Cite

168

167

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Insects are utterly reliant on sensory mechanotransduction, the process of converting physical stimuli into neuronal receptor potentials. The senses of proprioception, touch, and hearing are involved in almost every aspect of an adult insect's complex behavioral repertoire and are mediated by a diverse array of specialized sensilla and sensory neurons. The physiology and morphology of several of these have been described in detail; genetic approaches in Drosophila, combining behavioral screens and sensory electrophysiology with forward and reverse genetic techniques, have now revealed specific proteins involved in their differentiation and operation. These include three different TRP superfamily ion channels that are required for transduction in tactile bristles, chordotonal stretch receptors, and polymodal nociceptors. Transduction also depends on the normal differentiation and mechanical integrity of the modified cilia that form the neuronal sensory endings, the accessory structures that transmit stimuli to them and, in bristles, a specialized receptor lymph and transepithelial potential. Flies hear near-field sounds with a vibration-sensitive, antennal chordotonal organ. Biomechanical analyses of wild-type antennae reveal non-linear, active mechanical properties that increase their sensitivity to weak stimuli. The effects of mechanosensory and ciliary mutations on antennal mechanics show that the sensory cilia are the active motor elements and indicate distinct roles for TRPN and TRPV channels in auditory transduction and amplification.

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Intraflagellar Transport Is Required in Drosophila to Differentiate Sensory Cilia but Not Sperm

Abstract: NOMPB, the Drosophila homolog of IFT88, is required for the assembly of sensory cilia but not for the extension or function of the sperm flagellum. Assembly of this extremely long axoneme is therefore independent of IFT.

Cited by 210 publications

References 56 publications

Bardet–Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly

Bardet–Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly

yuri gagarinis required for actin, tubulin and basal body functions inDrosophilaspermatogenesis

Mechanotransduction and auditory transduction in Drosophila

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