RFX2 is broadly required for ciliogenesis during vertebrate development

Chung, Mei I.; Peyrot, Sara M.; LeBoeuf, Sarah E.; Park, Tae Joo; McGary, Kriston L.; Marcotte, Edward M.; Wallingford, John B.

doi:10.1016/j.ydbio.2011.12.029

Cited by 101 publications

(131 citation statements)

References 66 publications

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“…4A). The increased expression of these genes, along with key transcription factors for ciliogenesis such as foxj1a, foxj1b and rfx2 (Bisgrove et al, 2012;Chung et al, 2012;Stubbs et al, 2008;Yu et al, 2008), was confirmed by QRT-PCR ( Fig. 4B) and WISH (supplementary material Fig.…”

Section: Mir-34b Regulates Kidney Morphogenesis By Controlling Multicmentioning

confidence: 77%

miR-34b regulates multiciliogenesis during organ formation in zebrafish

Wang

Fan

et al. 2013

Development

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SUMMARYMulticiliated cells (MCCs) possess multiple motile cilia and are distributed throughout the vertebrate body, performing important physiological functions by regulating fluid movement in the intercellular space. Neither their function during organ development nor the molecular mechanisms underlying multiciliogenesis are well understood. Although dysregulation of members of the miR-34 family plays a key role in the progression of various cancers, the physiological function of miR-34b, especially in regulating organ formation, is largely unknown. Here, we demonstrate that miR-34b expression is enriched in kidney MCCs and the olfactory placode in zebrafish. Inhibiting miR-34b function using morpholino antisense oligonucleotides disrupted kidney proximal tubule convolution and the proper distribution of distal transporting cells and MCCs. Microarray analysis of gene expression, cilia immunostaining and a fluid flow assay revealed that miR-34b is functionally required for the multiciliogenesis of MCCs in the kidney and olfactory placode. We hypothesize that miR-34b regulates kidney morphogenesis by controlling the movement and distribution of kidney MCCs and fluid flow. We found that cmyb was genetically downstream of miR-34b and acted as a key regulator of multiciliogenesis. Elevated expression of cmyb blocked membrane docking of centrioles, whereas loss of cmyb impaired centriole multiplication, both of which resulted in defects in the formation of ciliary bundles. Thus, miR-34b serves as a guardian to maintain the proper level of cmyb expression. In summary, our studies have uncovered an essential role for miR-34b-Cmyb signaling during multiciliogenesis and kidney morphogenesis.

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Section: Mir-34b Regulates Kidney Morphogenesis By Controlling Multicmentioning

confidence: 77%

miR-34b regulates multiciliogenesis during organ formation in zebrafish

Wang

Fan

et al. 2013

Development

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“…Rfx2 is preferentially expressed in ciliated tissues such as the brain, organs of laterality, kidneys and testis from early development (Bisgrove et al, 2012;Chung et al, 2012;Horvath et al, 2004;Liu et al, 2007;Ma and Jiang, 2007;Thisse et al, 2004;Wolfe et al, 2004). In addition, rfx2 expression is enriched in motile multiciliated cells that differentiate in the epidermis of Xenopus larvae and within the pronephric kidney tubules of the zebrafish embryo -these cells are similar to motile multiciliated cells of the mammalian airways (Chung et al, 2012;Liu et al, 2007;Ma and Jiang, 2007).…”

Section: Rfx2mentioning

confidence: 99%

Switching on cilia: transcriptional networks regulating ciliogenesis

et al. 2014

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Cilia play many essential roles in fluid transport and cellular locomotion, and as sensory hubs for a variety of signal transduction pathways. Despite having a conserved basic morphology, cilia vary extensively in their shapes and sizes, ultrastructural details, numbers per cell, motility patterns and sensory capabilities. Emerging evidence indicates that this diversity, which is intimately linked to the different functions that cilia perform, is in large part programmed at the transcriptional level. Here, we review our understanding of the transcriptional control of ciliary biogenesis, highlighting the activities of FOXJ1 and the RFX family of transcriptional regulators. In addition, we examine how a number of signaling pathways, and lineage and cell fate determinants can induce and modulate ciliogenic programs to bring about the differentiation of distinct cilia types.

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“…No cilia-like structures were observed in kidney field explants, whereas they were readily detected in the GRP. In order to further attempt to detect cilia, we expressed an mCherry-tagged version of the axoneme protein arl13b (Borovina et al, 2010;Caspary et al, 2007;Chung et al, 2012), and analyzed its distribution in kidney field and GRP cells at NF stage 14. mCherry-arl13b was clearly localized in GRP cilia but never in kidney field cells (supplementary material Fig. S2).…”

Section: Resultsmentioning

confidence: 99%

TRPP2-dependent Ca2+ signaling in dorso-lateral mesoderm is required for kidney field establishment inXenopus

Futel

Leclerc

Buisson

et al. 2015

Journal of Cell Science

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In Xenopus laevis embryos, kidney field specification is dependent on retinoic acid (RA) and coincides with a dramatic increase of Ca 2+ transients, but the role of Ca 2+ signaling in the kidney field is unknown. Here, we identify TRPP2, a member of the transient receptor potential (TRP) superfamily of channel proteins encoded by the pkd2 gene, as a central component of Ca 2+ signaling in the kidney field. TRPP2 is strongly expressed at the plasma membrane where it might regulate extracellular Ca 2+ entry. Knockdown of pkd2 in the kidney field results in the downregulation of pax8, but not of other kidney field genes (lhx1, osr1 and osr2). We further show that inhibition of Ca 2+ signaling with an inducible Ca 2+ chelator also causes downregulation of pax8, and that pkd2 knockdown results in a severe inhibition of Ca 2+ transients in kidney field explants. Finally, we show that disruption of RA results both in an inhibition of intracellular Ca 2+ signaling and of TRPP2 incorporation into the plasma membrane of kidney field cells. We propose that TRPP2-dependent Ca 2+ signaling is a key component of pax8 regulation in the kidney field downstream of RA-mediated nontranscriptional control of TRPP2.

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RFX2 is broadly required for ciliogenesis during vertebrate development

Cited by 101 publications

References 66 publications

miR-34b regulates multiciliogenesis during organ formation in zebrafish

miR-34b regulates multiciliogenesis during organ formation in zebrafish

Switching on cilia: transcriptional networks regulating ciliogenesis

TRPP2-dependent Ca2+ signaling in dorso-lateral mesoderm is required for kidney field establishment inXenopus

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