Cdc42 Mediates Bmp-Induced Sprouting Angiogenesis through Fmnl3-Driven Assembly of Endothelial Filopodia in Zebrafish

Wakayama, Yuki; Fukuhara, Shigetomo; Ando, Koji; Matsuda, Minoru; Mochizuki, Naoki

doi:10.1016/j.devcel.2014.11.024

Cited by 145 publications

(146 citation statements)

References 32 publications

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“…Again, weaker binding was found for GTP-Rac1 with about a fourfold enrichment over GDP-Rac1 ( Figure 4C; quantified in Figure 4E). These findings are consistent with human FMNL1/2 or zebrafish Fmnl3 activation by Cdc42 (Block et al 2012;Kuhn et al 2015;Richards et al 2015;Wakayama et al 2015) and mouse Frl1/Fmnl1 showing a weak preference for Rac-GTP over Rac-GDP, although the latter failed to bind Cdc42 (Yayoshi-Yamamoto et al 2000).…”

Section: Frl Is Regulated By Cdc42 In Vivosupporting

confidence: 79%

Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila

et al. 2016

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The noncanonical Frizzled/planar cell polarity (PCP) pathway regulates establishment of polarity within the plane of an epithelium to generate diversity of cell fates, asymmetric, but highly aligned structures, or to orchestrate the directional migration of cells during convergent extension during vertebrate gastrulation. In Drosophila, PCP signaling is essential to orient actin wing hairs and to align ommatidia in the eye, in part by coordinating the movement of groups of photoreceptor cells during ommatidial rotation. Importantly, the coordination of PCP signaling with changes in the cytoskeleton is essential for proper epithelial polarity. Formins polymerize linear actin filaments and are key regulators of the actin cytoskeleton. Here, we show that the diaphanous-related formin, Frl, the single fly member of the FMNL (formin related in leukocytes/formin-like) formin subfamily affects ommatidial rotation in the Drosophila eye and is controlled by the Rho family GTPase Cdc42. Interestingly, we also found that frl mutants exhibit an axon growth phenotype in the mushroom body, a center for olfactory learning in the Drosophila brain, which is also affected in a subset of PCP genes. Significantly, Frl cooperates with Cdc42 and another formin, DAAM, during mushroom body formation. This study thus suggests that different formins can cooperate or act independently in distinct tissues, likely integrating various signaling inputs with the regulation of the cytoskeleton. It furthermore highlights the importance and complexity of formin-dependent cytoskeletal regulation in multiple organs and developmental contexts.

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Section: Frl Is Regulated By Cdc42 In Vivosupporting

confidence: 79%

Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila

et al. 2016

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“…In summary, although Mogat1 expression is highly upregulated in fatty livers of lipodystrophic ( Agpat2 Ϫ / Ϫ ) and ob / ob oligonucleotide approaches in an acute experimental setting bring about reduced liver TAG and improved IR and type 2 diabetes mellitus . A recent study, although not related to the metabolic studies discussed here, reported that the use of antisense technology and genetic deletion resulted in widely different phenotypes (33)(34)(35). We interpret our study with an additional caution.…”

Section: Mogat1contrasting

confidence: 41%

Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2−/−) or obese (ob/ob) mice

Agarwal

Tunison

Dalal

et al. 2016

Journal of Lipid Research

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“…For knockdown of tuba and cdc42, three antisense morpholino (MO) oligonucleotides that block translation or splicing were designed, targeting the ATG start codon or a splice donor site of exon 5 in tuba, and purchased from Gene Tools, LLC: tuba AUG MO (5Ј-ACCACCGAGCCAGCCTC-CATGTTCA-3Ј), tuba splice site MO (5Ј-AGCTGGG ATT-TACAGACCTGTTTCT-3Ј), and cdc42 AUG-MO (5Ј-CAAC-GACGCACTTGATCGTCTGC AT-3Ј). Knockdown of two control GEFs, Obscurin and Fgd5, was performed using the splice site morpholinos (25,26). The scrambled control oligo purchased from Gene Tools was used as a negative control, and the total amount of MO injected under each condition was kept equivalent for the control MOs.…”

Section: Methodsmentioning

confidence: 99%

“…4F). To ensure specificity of the tuba MOs, we additionally performed a side-by-side morpholino analysis targeting two other GEFs, Obscurin and Fgd5, which are not known to be involved in the Cdc42-mediated ciliogenesis pathway (25,26), in addition to the scrambled control MOs (Fig. 4F).…”

Section: Tuba Localizes To Ciliated Organs and Depletion Of Tuba Caumentioning

confidence: 99%

Dynamin Binding Protein (Tuba) Deficiency Inhibits Ciliogenesis and Nephrogenesis in Vitro and in Vivo

Baek¹,

Kwon²,

Zuo³

et al. 2016

Journal of Biological Chemistry

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Dysfunction of renal primary cilia leads to polycystic kidney disease. We previously showed that the exocyst, a protein trafficking complex, is essential for ciliogenesis and regulated by multiple Rho and Rab family GTPases, such as Cdc42. Cdc42 deficiency resulted in a disruption of renal ciliogenesis and a polycystic kidney disease phenotype in zebrafish and mice. Here we investigate the role of Dynamin binding protein (also known as Tuba), a Cdc42-specific guanine nucleotide exchange factor, in ciliogenesis and nephrogenesis using Tuba knockdown Madin-Darby canine kidney cells and tuba knockdown in zebrafish. Tuba depletion resulted in an absence of cilia, with impaired apical polarization and inhibition of hepatocyte growth factor-induced tubulogenesis in Tuba knockdown Madin-Darby canine kidney cell cysts cultured in a collagen gel. In zebrafish, tuba was expressed in multiple ciliated organs, and, accordingly, tuba start and splice site morphants showed various ciliary mutant phenotypes in these organs. Co-injection of tuba and cdc42 morpholinos at low doses, which alone had no effect, resulted in genetic synergy and led to abnormal kidney development with highly disorganized pronephric duct cilia. Morpholinos targeting two other guanine nucleotide exchange factors not known to be in the Cdc42/ciliogenesis pathway and a scrambled control morpholino showed no phenotypic effect. Given the molecular nature of Cdc42 and Tuba, our data strongly suggest that tuba and cdc42 act in the same ciliogenesis pathway. Our study demonstrates that Tuba deficiency causes an abnormal renal ciliary and morphogenetic phenotype. Tuba most likely plays a critical role in ciliogenesis and nephrogenesis by regulating Cdc42 activity.

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Cdc42 Mediates Bmp-Induced Sprouting Angiogenesis through Fmnl3-Driven Assembly of Endothelial Filopodia in Zebrafish

Cited by 145 publications

References 32 publications

Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila

Unique and Overlapping Functions of Formins Frl and DAAM During Ommatidial Rotation and Neuronal Development in Drosophila

Mogat1 deletion does not ameliorate hepatic steatosis in lipodystrophic (Agpat2−/−) or obese (ob/ob) mice

Dynamin Binding Protein (Tuba) Deficiency Inhibits Ciliogenesis and Nephrogenesis in Vitro and in Vivo

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