TEAM

Biology of ciliated epithelia

Group leader : L. Kodjabachian

Presentation
Publications

Our team aims to understand ciliated epithelia biology.

FOR BEGINNERS

In all vertebrates, specialized ciliated tissues are covered with cells harboring dozens of motile cilia, beating coordinately to generate directional fluid flow. Multiciliated cells help airway cleansing, ovum implantation and cerebrospinal fluid circulation.

Scanning Electron Microscopy photograph of the mature ciliated epidermis. Green: Multiciliated cell. Red: Mucus secretory cell (also called goblet cell). Dark brown: Smal secretory cell (produces serotonin). Yellow: Ionocyte.

Thus, several human pathologies caused by ciliary defects are characterized by chronic respiratory distress, brain abnormalities and reduced fertility. However, the biology of multiciliated cells remains poorly understood, due to the paucity of accessible in vivo models. Our team studies the embryonic skin of the amphibian Xenopus laevis, which is proving very powerful to reveal molecular and cellular principles of multiciliogenesis conserved with humans.

The Xenopus laevis embryo is easily amenable to manipulation of protein-coding genes as well as non-coding RNAs (microRNAs, long non coding RNAs) through micro-injection of mRNA constructs or antisense morpholinos, from the time of fertilization. The ciliated epidermis is particularly suited for functional analysis as it can be targeted specifically and lies at the surface of the embryo, which facilitates light and electron microscopy imaging. This tissue can also easily be exposed to pharmacological compounds and recombinant proteins at various stages of its development, and subjected to transgenesis to trace and manipulate the various cell types that compose it.

FOR SPECIALISTS

This picture shows the epidermis of a xenope tailbud-stage embryo, allowing study of ciliogenesis.

Transverse section through the epidermis of a tailbud-stage embryo. Nuclei are stained with DAPI in blue. Basal cells are stained by immunostaining against P63 in white. Multiciliated cells are stained by fluorescent in situ hybridization against alpha-tubulin in green. Ionocytes are stained by fluorescent in situ hybridization against the ATPase V1A in red.

Ciliogenesis has emerged as a key biological phenomenon in many developmental and physiological processes. Deficient ciliogenesis is the cause of numerous diseases, collectively called ciliopathies. Cilia can be motile and help generate biological fluid flows, or immotile and function as sensing and signalling platforms. Ciliogenesis is a complex process, which mobilizes several hundreds of distinct proteins. Additional complexity is coming with the differentiation into multiciliated cells that require a dramatic reorganization of the microtubular network and a 20-fold increase in the apical cell membrane.

In certain chronic airway diseases, regeneration of a functional mucociliary epithelium is important for proper healing. From this prospect, understanding the mechanisms governing the biosynthesis of multiciliated cells is a fundamental issue with high biomedical relevance.

The embryonic Xenopus laevis epidermis contains a mucociliary epithelium similar to the one covering our airways. In both cases, the epithelium is composed of mucus-secreting cells and of multiciliated cells, and represents the first line of defense against germs and pollutants. In Xenopus, the mature epithelium is set in place through four successive steps :

The four steps of ciliated epithelium formation.

Our team currently studies steps 2 to 4: i. specification of the various cell types present in the epidermis. ii. insertion of ciliated cell precursors in the superficial epithelial layer. iii. differentiation of multiciliated cells. We focus on the roles in these processes of signalling pathways and microRNAs, as the former often control cell fate decisions whereas the latter often control developmental transitions and differentiation. Our long-term goal is to generate an integrated view of the key mechanisms necessary to build and maintain the functional mucociliary epithelium that are conserved in humans.

Selected publications

PUBLICATION

November 7th, 2018

CDC20B is required for deuterosome-mediated centriole production in multiciliated cells.

Revinski, DR^†., Zaragosi, L-E^†., Boutin, C^†., Ruiz Garcia, S., Deprez, M., Rosnet, O., Thomé, V., Mercey, O., Paquet, A., Pons, N., Marcet, B^*., Kodjabachian, L^*. and Barbry, P^*. Equal contribution^†, corresponding authors^*.

Nature Communications. 9:4668. PMID: 30405130

Biology of ciliated epithelia

Group leader : L. Kodjabachian

FOR BEGINNERS

FOR SPECIALISTS

Selected publications

CDC20B is required for deuterosome-mediated centriole production in multiciliated cells.

Lineage commitment of embryonic cells involves MEK1-dependent clearance of pluripotency regulator Ventx2.

BMP signalling controls the construction of vertebrate mucociliary epithelia.

Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.

BMP inhibition initiates neural induction via FGF signaling and Zic genes.

Notch1 is asymmetrically distributed from the beginning of embryogenesis and controls the ventral center

A Bioresistant Nitroxide Spin Label for In-Cell EPR Spectroscopy: In Vitro and In Oocytes Protein Structural Dynamics Studies.

Animal multicellularity and polarity without Wnt signaling.

Nodal–Activin pathway is a conserved neural induction signal in chordates

Planar cell polarity in ciliated epithelia.

Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signalling in breast cancer.

The PTK7 and ROR2 Protein Receptors Interact in the Vertebrate WNT/Planar Cell Polarity (PCP) Pathway

miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways

Induction and Differentiation of the Xenopus Ciliated Embryonic Epidermis.

Dysregulation of Wnt Inhibitory Factor 1 (Wif1) expression result in aberrant Wnt-β-catenin signaling and cell death of the cloaca endoderm, and anorectal malformations.

Xenopus embryonic epidermis as a mucociliary cellular ecosystem to assess the effect of sex hormones in a non-reproductive context.

On the Origin and Evolutionary History of NANOG.

A gene regulation network controlled by Celf1 protein-rbpj mRNA interaction in Xenopus somite segmentation.

The human PDZome: a gateway to PDZ mediated functions.

Ventx factors function as Nanog-like guardians of developmental potential in Xenopus.

An essential role for transcription before the MBT in Xenopus laevis.

MicroRNA-based silencing of Delta/Notch signaling promotes multiple cilia formation.

MicroRNA control biosynthesis of motile cilia in vertebrates.

PTK7: a cell polarity receptor with multiple facets.

Protein tyrosine kinase 7 has a conserved role in Wnt/β-catenin canonical signalling.

Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control gastrulation movements in parallel to the Wnt/PCP pathway.

Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice.

Neural induction in Xenopus requires early FGF signalling in addition to BMP inhibition.

Role of Siamois before and during gastrulation. In Gastrulation : From cells to embryo

Siamois functions in the early blastula to induce Spemann's organiser.

Morphogen gradients: nodal enters the stage.

A study of Xlim1 function in the Spemann-Mangold organizer.

A new secreted protein that binds to Wnt proteins and inhibits their activities.

Embryonic induction: is the Nieuwkoop centre a useful concept?

A role for the vegetally expressed Xenopus gene Mix.1 in endoderm formation and in the restriction of mesoderm to the marginal zone.

Mutations in ccf, a novel Drosophila gene encoding a chromosomal factor, affect progression through mitosis and interact with Pc-G mutations.

The vertebrate organizer: structure and molecules.

The homeobox gene Siamois is a target of the Wnt dorsalisation pathway and triggers organiser activity in the absence of mesoderm.

Research

Keywords

Interactions

IBDM

NATIONAL

Funding

Members more

Laurent Kodjabachian

Camille Boutin

Alexandre Chuyen

Aude Nommick

Andrea Pasini

Diego Revinski

Olivier Rosnet

Virginie Thome

Marie Zilliox

Alumni

Overview

Model organism

Biological process studied

Biological techniques

Links