Biology of ciliated epithelia
Group leader : L. Kodjabachian
Our team aims to understand ciliated epithelia biology.
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.
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.
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 :
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.
November 7th, 2018
CDC20B is required for deuterosome-mediated centriole production in multiciliated cells.
June 27th, 2017
Lineage commitment of embryonic cells involves MEK1-dependent clearance of pluripotency regulator Ventx2.
July 9th, 2015
BMP signalling controls the construction of vertebrate mucociliary epithelia.
June 1st, 2011
Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
October 13th, 2009
BMP inhibition initiates neural induction via FGF signaling and Zic genes.
July 17th, 2018
Notch1 is asymmetrically distributed from the beginning of embryogenesis and controls the ventral center
January 26th, 2018
A Bioresistant Nitroxide Spin Label for In-Cell EPR Spectroscopy: In Vitro and In Oocytes Protein Structural Dynamics Studies.
November 13th, 2017
Animal multicellularity and polarity without Wnt signaling.
July 3rd, 2017
Nodal–Activin pathway is a conserved neural induction signal in chordates
January 13th, 2017
Planar cell polarity in ciliated epithelia.
January 12th, 2016
Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signalling in breast cancer.
December 18th, 2015
The PTK7 and ROR2 Protein Receptors Interact in the Vertebrate WNT/Planar Cell Polarity (PCP) Pathway
September 21st, 2015
miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways
May 13th, 2014
Induction and Differentiation of the Xenopus Ciliated Embryonic Epidermis.
March 6th, 2014
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.
February 6th, 2014
Xenopus embryonic epidermis as a mucociliary cellular ecosystem to assess the effect of sex hormones in a non-reproductive context.
January 17th, 2014
On the Origin and Evolutionary History of NANOG.
August 30th, 2013
A gene regulation network controlled by Celf1 protein-rbpj mRNA interaction in Xenopus somite segmentation.
May 30th, 2013
The human PDZome: a gateway to PDZ mediated functions.
January 1st, 2012
Ventx factors function as Nanog-like guardians of developmental potential in Xenopus.
September 15th, 2011
An essential role for transcription before the MBT in Xenopus laevis.
September 1st, 2011
MicroRNA-based silencing of Delta/Notch signaling promotes multiple cilia formation.
June 1st, 2011
MicroRNA control biosynthesis of motile cilia in vertebrates.
January 15th, 2011
PTK7: a cell polarity receptor with multiple facets.
January 1st, 2011
Protein tyrosine kinase 7 has a conserved role in Wnt/β-catenin canonical signalling.
February 1st, 2010
Distinct Xenopus Nodal ligands sequentially induce mesendoderm and control gastrulation movements in parallel to the Wnt/PCP pathway.
April 1st, 2009
Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice.
January 1st, 2005
Neural induction in Xenopus requires early FGF signalling in addition to BMP inhibition.
January 1st, 2004
Role of Siamois before and during gastrulation. In Gastrulation : From cells to embryo
Kodjabachian L, and Lemaire P.
October 1st, 2001
Siamois functions in the early blastula to induce Spemann's organiser.
August 21st, 2001
Morphogen gradients: nodal enters the stage.
January 1st, 2001
A study of Xlim1 function in the Spemann-Mangold organizer.
April 1st, 1999
A new secreted protein that binds to Wnt proteins and inhibits their activities.
December 17th, 1998
Embryonic induction: is the Nieuwkoop centre a useful concept?
July 1st, 1998
A role for the vegetally expressed Xenopus gene Mix.1 in endoderm formation and in the restriction of mesoderm to the marginal zone.
February 16th, 1998
Mutations in ccf, a novel Drosophila gene encoding a chromosomal factor, affect progression through mitosis and interact with Pc-G mutations.
December 1st, 1996
The vertebrate organizer: structure and molecules.
October 1st, 1996