AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment

Xu, Juan; Wan, Ping; Wang, M; Zhang, Jiahan; Gao, Xiang; Hu, Boqiang; Han, Jinxiong; Chen, L; Sun, Kaixuan; Wu, Ji; Wu, Xin; Huang, Xinyi; Chen, J

doi:10.1038/cddis.2015.182

Cited by 27 publications

(29 citation statements)

References 65 publications

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“…Consistently, Wdr1 KO blastocysts can hatch and adhere, but have impaired outgrowth and cannot be labeled with EdU, accompanying the severe defects of actin cytoskeleton. Wdr1 KO MEF cells have growth defects such as losing S phase and abnormal actin plaques, similar to the phenotypes observed in Wdr1-specific KO cardiomyocytes and sertoli cells (30,31). For successful development, mouse trophoblast cells dramatically differentiate and proliferate, accompanying tremendous changes in cytoskeleton after implantation (39,40).…”

Section: Discussionmentioning

confidence: 79%

“…WDR1 and its involvement in actin cytoskeleton play important roles in multiple processes during mouse development (27,30,31). However, the role of WDR1 in mouse early embryogen- esis is still largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…A Gene-trap vector inserted Wdr1 intron 2 disrupts its expression completely and results in embryonic lethality before E10.5 (embryonic day * This work was supported by National Natural Science Foundation of China 10.5) in mice, whereas a hypomorphic insertion mutation in this gene leads to autoinflammatory disease because of the impairment of cytoskeletal response in neutrophils and thrombopoiesis (27). WDR1-mediated actin disassembly is also required for spermatogenesis and myocardial growth in mice (30,31). In humans, the aberrant expressions of WDR1 have been shown to be connected to several diseases, including gout, pancreatitis, and primary glioblastoma (32)(33)(34).…”

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confidence: 99%

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Trp-Asp (WD) Repeat Domain 1 Is Essential for Mouse Peri-implantation Development and Regulates Cofilin Phosphorylation

Xiao

Wan

et al. 2017

Journal of Biological Chemistry

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Edited by Xiao-Fan WangTrp-Asp (WD) repeat domain 1 (WDR1) is a highly conserved actin-binding protein across all eukaryotes and is involved in numerous actin-based processes by accelerating Cofilin severing actin filament. However, the function and the mechanism of WDR1 in mammalian early development are still largely unclear. We now report that WDR1 is essential for mouse periimplantation development and regulates Cofilin phosphorylation in mouse cells. The disruption of maternal WDR1 does not obviously affect ovulation and female fertility. However, depletion of zygotic WDR1 results in embryonic lethality at the periimplantation stage. In WDR1 knock-out cells, we found that WDR1 regulates Cofilin phosphorylation. Interestingly, WDR1 is overdosed to regulate Cofilin phosphorylation in mouse cells. Furthermore, we showed that WDR1 interacts with Lim domain kinase 1 (LIMK1), a well known phosphorylation kinase of Cofilin. Altogether, our results provide new insights into the role and mechanism of WDR1 in physiological conditions.The actin cytoskeleton is a highly dynamic structure that regulates cell motility, adhesion, division, and growth and has a fundamental function in embryonic development (1-3). In physiological conditions, actin filaments are continually assembled and disassembled in response to varied cellular activities (4, 5). The dynamics of F-actin is well orchestrated by a large number of actin-binding proteins (5, 6). Actin-depolymerizing factor Cofilin plays critical roles in the modulation of actin cytoskeleton dynamics (7). In vitro, Cofilin severs actin filament at low concentrations, whereas it fully decorates actin filaments and suppresses the severing activity at high concentrations (8, 9). In addition, Cofilin severing F-actin is not explained well for how the filaments of actin cytoskeleton can be rapidly disassembled in physiological conditions (4). Thus, the function of Cofilin in actin dynamics depends not only on its relative concentration to actin, but also on other regulatory proteins in vivo. Dysfunction of these regulating proteins results in aberrant actin cytoskeleton in various cellular and developmental processes (10 -12).Cofilin directly binds with actin to function as a regulator of the actin dynamics (13). However, the phosphorylation of Cofilin at Ser-3 blocks its binding site to actin (14, 15). Thus, the activity of Cofilin is controlled by phosphorylation and dephosphorylation processes, which are regulated by cascade reactions of several protein kinases and phosphatases. Lim domain kinases (LIMKs) 4 and testis-specific protein kinases (TESKs) are responsible for the phosphorylation of Cofilin, whereas slingshot (SSH) family protein phosphatases and pyridoxal phosphatase (PDXP) catalyze the dephosphorylation reaction (16 -20). These kinases and phosphatases are also regulated by their phosphorylation or localization in cytoplasm to maintain the level of Cofilin phosphorylation in response to extracellular stimuli (21-23).The activity of Cofilin on actin disassembly is gr...

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Trp-Asp (WD) Repeat Domain 1 Is Essential for Mouse Peri-implantation Development and Regulates Cofilin Phosphorylation

Xiao

Wan

et al. 2017

Journal of Biological Chemistry

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“…Among them, Pdgfrb and Dab2ip , have been directly shown to drive ProSG migration in neonatal testes (Basciani et al, 2008; Xu et al, 2015). Of note, Pdgfrb not only promotes ProSG migration but also the accompanying step, resumption of ProSG proliferation (Basciani et al, 2008; Payne, 2013; Thuillier et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment

Song

Bettegowda

Lake³

et al. 2016

Cell Reports

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Summary The developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor—RHOX10—that is critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. Using a battery of approaches, including single cell-RNAseq (scRNAseq) analysis, we show that Rhox10 drives SSC generation by promoting Pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of Pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general.

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“…1). The migration of germ cells into, and the maintenance of cell-cell interactions within, the niche relies on integrin and actin-based adhesion junctions (Kanatsu-Shinohara et al 2008) and key actin regulators (Carlomagno et al 2010, Xu et al 2015. Reports that gonocytes and SSCs exhibit a polarized enrichment of α-tubulin and acetylated α-tubulin towards the basement membrane (Steger & Wrobel 1994, Luo et al 2010) also suggests microtubules aid in orienting and maintaining cells within the niche, particularly as tubulin acetylation correlates with decreased cell motility (Hubbert et al 2002).…”

Section: Actinmentioning

confidence: 99%

The cytoskeleton in spermatogenesis

et al. 2019

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As germ cells progress through spermatogenesis, they undergo a dramatic transformation, wherein a single, diploid spermatogonial stem cell ultimately produces thousands of highly specialised, haploid spermatozoa. The cytoskeleton is an integral aspect of all eukaryotic cells. It concomitantly provides both structural support and functional pliability, performing key roles in many fundamental processes including, motility, intracellular trafficking, differentiation and cell division. Accordingly, cytoskeletal dynamics underlie many key spermatogenic processes. This review summarises the organisational and functional aspects of the four major cytoskeletal components (actin, microtubules, intermediate filaments and septins) during the various spermatogenic phases in mammals. We focus on the cytoskeletal machinery of both germ cells and Sertoli cells, and thus, highlight the critical importance of a dynamic and precisely regulated cytoskeleton for male fertility.

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AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment

Cited by 27 publications

References 65 publications

Trp-Asp (WD) Repeat Domain 1 Is Essential for Mouse Peri-implantation Development and Regulates Cofilin Phosphorylation

Trp-Asp (WD) Repeat Domain 1 Is Essential for Mouse Peri-implantation Development and Regulates Cofilin Phosphorylation

The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment

The cytoskeleton in spermatogenesis

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