Germ Cell Intercellular Bridges

Greenbaum, Michael P.; Iwamori, Tokuko; Buchold, Gregory M.; Matzuk, Martin M.

doi:10.1101/cshperspect.a005850

Cited by 208 publications

(213 citation statements)

References 109 publications

(154 reference statements)

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“…Upon loss of Src64 function, the closed RCs, altered signaling in germ or somatic cells and/or impaired fusome development may contribute to disrupting cyst synchrony. Male germline RCs are thought to promote intercellular germ cell communication and synchronization of, for example, mitotic germ cell divisions (Greenbaum et al, 2011;Haglund et al, 2011). However, the cell biological and developmental roles of RCs in male germline cysts remain elusive (Greenbaum et al, 2011;Haglund et al, 2011) and it will be important to address the physiological consequences of smaller RCs in germline cysts.…”

Section: Loss Of Src64 Results In Asynchronous Tumors In the Drosophimentioning

confidence: 99%

“…RCs are required for fertility in both insects and mammals, but current knowledge of the regulation of these structures is limited (Robinson et al, 1994;Haglund et al, 2011). The scaffolding molecules Anillin and Cindr, the central spindle component Pavarotti, as well as actin and myosin have been shown to localize to RCs (Field and Alberts, 1995;Hime et al, 1996;Adams et al, 1998;Haglund et al, 2010;Eikenes et al, 2013), but little is known about the molecular mechanisms regulating incomplete cytokinesis in vivo Greenbaum et al, 2011;Haglund et al, 2011;Mathieu et al, 2013;Yamamoto et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Germ cell divisions in the Drosophila female and male germlines occur with incomplete cytokinesis, resulting in the formation of cysts in which germ cells are interconnected via stable intercellular bridges called ring canals (RCs) (Hime et al, 1996;Robinson and Cooley, 1996;Greenbaum et al, 2011) (Fig. 1A).…”

Section: Introductionmentioning

confidence: 99%

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Src64 controls a novel actin network required for proper ring canal formation in the Drosophila male germline

et al. 2015

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In many organisms, germ cells develop as cysts in which cells are interconnected via ring canals (RCs) as a result of incomplete cytokinesis. However, the molecular mechanisms of incomplete cytokinesis remain poorly understood. Here, we address the role of tyrosine phosphorylation of RCs in the Drosophila male germline. We uncover a hierarchy of tyrosine phosphorylation within germline cysts that positively correlates with RC age. The kinase Src64 is responsible for mediating RC tyrosine phosphorylation, and loss of Src64 causes a reduction in RC diameter within germline cysts. Mechanistically, we show that Src64 controls an actin network around the RCs that depends on Abl and the Rac/SCAR/Arp2/3 pathway. The actin network around RCs is required for correct RC diameter in cysts of developing germ cells. We also identify that Src64 is required for proper germ cell differentiation in the Drosophila male germline independent of its role in RC regulation. In summary, we report that Src64 controls actin dynamics to mediate proper RC formation during incomplete cytokinesis during germline cyst development in vivo.

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Section: Loss Of Src64 Results In Asynchronous Tumors In the Drosophimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Src64 controls a novel actin network required for proper ring canal formation in the Drosophila male germline

et al. 2015

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“…Less is known about the structure and function of murine cysts, but organelles also move through cyst bridges (Pepling and Spradling, 2001) and a Balbiani body is present in young primordial follicles (Pepling et al, 2007). Mice deficient for the intercellular bridge protein TEX14 contain nested germ cells that no longer seem to be interconnected, but only males are sterile (Greenbaum et al, 2006;Greenbaum et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Mouse primordial germ cells produce cysts that partially fragment prior to meiosis

2013

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SUMMARYMammalian germ cells divide mitotically and form nests of associated cells just prior to entering meiosis. At least some nests contain germline cysts that arise by synchronous, incomplete mitotic divisions, but others may form by aggregation. To systematically investigate early murine germ cell development, we lineage marked the progeny of individual, newly arrived primordial germ cells in the E10.5 gonad. All the marked germ cells initially develop into clones containing two, four or eight cells, indicating cyst formation. Surprisingly, growing cysts in both sexes partially fragment into smaller cysts prior to completion and associate with cysts from unrelated progenitors. At the time divisions cease, female clones comprise five cysts on average that eventually give rise to about six primordial follicles. Male cyst cells break apart and probably become spermatogonial stem cells. Thus, cysts are invariant units of mouse germ cell development and cyst fragmentation provides insight into the amplification of spermatogonial stem cells and the origin of primordial follicles.

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“…This process is mainly driven by two-pre-and postmeiotictranscription waves that are tightly controlled by testis-specific transcription factors. During the premeiotic transcription phase, individual spermatogonia are committed to differentiating into primary spermatocytes that later undergo two meiotic divisions to generate haploid round spermatids connected by intercellular cytoplasmic bridges (1)(2)(3). During the postmeiotic transcription phase of spermiogenesis, haploid round spermatids are sculptured into the elongated shape of mature spermatozoa.…”

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confidence: 99%

Taf7l cooperates with Trf2 to regulate spermiogenesis

Zhou

Grubisic

Zheng

et al. 2013

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

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TATA-binding protein (TBP)-associated factor 7l (Taf7l; a paralogue of Taf7) and TBP-related factor 2 (Trf2) are components of the core promoter complex required for gene/tissue-specific transcription of protein-coding genes by RNA polymerase II. Previous studies reported that Taf7l knockout (KO) mice exhibit structurally abnormal sperm, reduced sperm count, weakened motility, and compromised fertility. Here we find that continued backcrossing of Taf7l −/Y mice from N5 to N9 produced KO males that are essentially sterile. Genome-wide expression profiling by mRNA-sequencing analysis of wild-type (WT) and Taf7l −/Y (KO) testes revealed that Taf7l ablation impairs the expression of many postmeiotic spermatogenic-specific as well as metabolic genes. Importantly, histological analysis of testes revealed that Taf7l −/Y mice develop postmeiotic arrest at the first stage of spermiogenesis, phenotypically similar to Trf2 −/− mice, but distinct from Taf4b −/− mice. Indeed, we find that Taf7l and Trf2 coregulate postmeiotic genes, but none of Taf4b-regulated germ stem cell genes in testes. Genome-wide ChIP-sequencing studies indicate that TAF7L binds to promoters of activated postmeiotic genes in testis. Moreover, biochemical studies show that TAF7L associates with TRF2 both in vitro and in testis, suggesting that TAF7L likely cooperates directly with TRF2 at promoters of a subset of postmeiotic genes to regulate spermiogenesis. Our findings thus provide a previously undescribed mechanism for cell-type-specific transcriptional control involving an interaction between a "nonprototypic" core promoter recognition factor (Trf2) and an orphan TAF subunit (Taf7l) in mammalian testis-specific gene transcription.gene regulation | reproduction | RNA-seq | contraceptive medicine S permatogenesis is a cyclic process in which diploid spermatogonia differentiate into mature haploid spermatozoa. This process is mainly driven by two-pre-and postmeiotictranscription waves that are tightly controlled by testis-specific transcription factors. During the premeiotic transcription phase, individual spermatogonia are committed to differentiating into primary spermatocytes that later undergo two meiotic divisions to generate haploid round spermatids connected by intercellular cytoplasmic bridges (1-3). During the postmeiotic transcription phase of spermiogenesis, haploid round spermatids are sculptured into the elongated shape of mature spermatozoa. These latter stages are accompanied by dramatic biochemical and morphological changes, including major remodeling of chromatin with protamines substituting for somatic histones to tightly pack DNA into the sperm nucleus.Understanding the intricate mechanisms that control spermatogenesis has important implications for human health and reproduction. A key step in the regulation of spermatogenesis occurs at the level of transcription, starting with the use of distinct promoter elements (4) within uniquely reorganized chromatin (5) and driven by the action of several testis-specific transcription factors...

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Germ Cell Intercellular Bridges

Cited by 208 publications

References 109 publications

Src64 controls a novel actin network required for proper ring canal formation in the Drosophila male germline

Src64 controls a novel actin network required for proper ring canal formation in the Drosophila male germline

Mouse primordial germ cells produce cysts that partially fragment prior to meiosis

Taf7l cooperates with Trf2 to regulate spermiogenesis

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