UCAGenomiX related publications

Du to our strong expertise in "omics" experiments and in microRNAs topics we decided to separate into 3 categories the related publications into which the Functional genomics Platform of Nice-Sophia-Antipolis is involved :
  1. Expression studies (DNA microarrays and high-throughput sequencing experiments)
  2. MicroRNA studies
  3. Miscellaneous

Mercey Olivier

 mercey@ipmc.cnrs.fr
 04 93 95 77 90
 660 route des lucioles 06560 Valbonne - Sophia-Antipolis

5 publications found

1. CDC20B is required for deuterosome-mediated centriole production in multiciliated cells
Nat Commun. 2018 Nov 7;9(1):4668. doi: 10.1038/s41467-018-06768-z.
Revinski DR, Zaragosi LE, Boutin C, Ruiz-Garcia S, Deprez M, Thomé V, Rosnet O, Gay AS, Mercey O, Paquet A, Pons N, Ponzio G, Marcet B, Kodjabachian L, Barbry P
Aix Marseille Univ, CNRS, IBDM, Marseille, France. Université Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France. Université Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France. marcet@ipmc.cnrs.fr. Aix Marseille Univ, CNRS, IBDM, Marseille, France. laurent.kodjabachian@univ-amu.fr. Université Côte d'Azur, CNRS, IPMC, Sophia-Antipolis, France. barbry@ipmc.cnrs.fr.

Multiciliated cells (MCCs) harbor dozens to hundreds of motile cilia, which generate hydrodynamic forces important in animal physiology. In vertebrates, MCC differentiation involves massive centriole production by poorly characterized structures called deuterosomes. Here, single-cell RNA sequencing reveals that human deuterosome stage MCCs are characterized by the expression of many cell cycle-related genes. We further investigated the uncharacterized vertebrate-specific cell division cycle 20B (CDC20B) gene, which hosts microRNA-449abc. We show that CDC20B protein associates to deuterosomes and is required for centriole release and subsequent cilia production in mouse and Xenopus MCCs. CDC20B interacts with PLK1, a kinase known to coordinate centriole disengagement with the protease Separase in mitotic cells. Strikingly, over-expression of Separase rescues centriole disengagement and cilia production in CDC20B-deficient MCCs. This work reveals the shaping of deuterosome-mediated centriole production in vertebrate MCCs, by adaptation of canonical and recently evolved cell cycle-related molecules.
Pubmed link : 30405130

2. Characterizing isomiR variants within the microRNA-34/449 family
FEBS Lett. 2017 Mar;591(5):693-705. doi: 10.1002/1873-3468.12595. Epub 2017 Feb 28
Mercey O, Popa A, Cavard A, Paquet A, Chevalier B, Pons N, Magnone V, Zangari J, Brest P, Zaragosi LE, Ponzio G, Lebrigand K, Barbry P, Marcet B
CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France. CNRS, INSERM, IRCAN, FHU-OncoAge, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.

miR-34/449 microRNAs are conserved regulators of multiciliated cell differentiation. Here, we evidence and characterize expression of two isomiR variant sequences from the miR-34/449 family in human airway epithelial cells. These isomiRs differ from their canonical counterparts miR-34b and miR-449c by one supplemental uridine at their 5'-end, leading to a one-base shift in their seed region. Overexpression of canonical miR-34/449 or 5'-isomiR-34/449 induces distinct gene expression profiles and biological effects. However, some target transcripts and functional activities are shared by both canonical microRNAs and isomiRs. Indeed, both repress important targets that result in cell cycle blockage and Notch pathway inhibition. Our findings suggest that 5'-isomiR-34/449 may represent additional mechanisms by which miR-34/449 family finely controls several pathways to drive multiciliogenesis.
Pubmed link : 28192603

3. MicroRNAs as key regulators of GTPase-mediated apical actin reorganization in multiciliated epithelia
Small GTPases. 2016 Apr 2;7(2):54-8. doi: 10.1080/21541248.2016.1151099.
Mercey O, Kodjabachian L, Barbry P, Marcet B
CNRS-IPMC, UMR-7275 , Sophia-Antipolis , France. University of Nice-Sophia-Antipolis (UNS) , Sophia-Antipolis , France. Aix-Marseille Université, CNRS, IBDM UMR7288 , Marseille , France.

Multiciliated cells (MCCs), which are present in specialized vertebrate tissues such as mucociliary epithelia, project hundreds of motile cilia from their apical membrane. Coordinated ciliary beating in MCCs contributes to fluid propulsion in several biological processes. In a previous work, we demonstrated that microRNAs of the miR-34/449 family act as new conserved regulators of MCC differentiation by specifically repressing cell cycle genes and the Notch pathway. Recently, we have shown that miR-34/449 also modulate small GTPase pathways to promote, in a later stage of differentiation, the assembly of the apical actin network, a prerequisite for proper anchoring of centrioles-derived neo-synthesized basal bodies. We characterized several miR-34/449 targets related to small GTPase pathways including R-Ras, which represents a key and conserved regulator during MCC differentiation. Direct RRAS repression by miR-34/449 is necessary for apical actin meshwork assembly, notably by allowing the apical relocalization of the actin binding protein Filamin-A near basal bodies. Our studies establish miR-34/449 as central players that orchestrate several steps of MCC differentiation program by regulating distinct signaling pathways.
Pubmed link : 27144998

4. miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways.
Nat Commun. 2015 Sep 18;6:8386. doi: 10.1038/ncomms9386.
Chevalier B, Adamiok A, Mercey O, Revinski DR, Zaragosi LE, Pasini A, Kodjabachian L, Barbry P, Marcet B
1CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR-7275, 660 route des Lucioles, 06560 Sophia-Antipolis, France. 2University of Nice-Sophia-Antipolis (UNS), Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Valbonne, 06560 Sophia-Antipolis, France. 3Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille, France.

Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways.
Pubmed link : 26381333

5. BMP signalling controls the construction of vertebrate mucociliary epithelia.
Development. 2015 Jul 1;142(13):2352-63. doi: 10.1242/dev.118679. Epub 2015 Jun 19.
Cibois M, Luxardi G, Chevalier B, Thomé V, Mercey O, Zaragosi LE, Barbry P, Pasini A, Marcet B, Kodjabachian L
1Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France. 2CNRS, IPMC, Sophia-Antipolis 06560, France. 3CNRS, IPMC, Sophia-Antipolis 06560, France University of Nice Sophia Antipolis (UNS), IPMC, Sophia-Antipolis 06560, France. 4Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France laurent.kodjabachian@univ-amu.fr.

Despite the importance of mucociliary epithelia in animal physiology, the mechanisms controlling their establishment are poorly understood. Using the developing Xenopus epidermis and regenerating human upper airways, we reveal the importance of BMP signalling for the construction of vertebrate mucociliary epithelia. In Xenopus, attenuation of BMP activity is necessary for the specification of multiciliated cells (MCCs), ionocytes and small secretory cells (SSCs). Conversely, BMP activity is required for the proper differentiation of goblet cells. Our data suggest that the BMP and Notch pathways interact to control fate choices in the developing epidermis. Unexpectedly, BMP activity is also necessary for the insertion of MCCs, ionocytes and SSCs into the surface epithelium. In human, BMP inhibition also strongly stimulates the formation of MCCs in normal and pathological (cystic fibrosis) airway samples, whereas BMP overactivation has the opposite effect. This work identifies the BMP pathway as a key regulator of vertebrate mucociliary epithelium differentiation and morphogenesis.
Pubmed link : 26092849