All Group Leaders 

Comparative studies of CNS development

Corinne Houart

Corinne Houart

Professor of Developmental Neurobiology

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Overview

The Houart lab has the ambition to understand the normal development of the vertebrate forebrain, with a focus on i) the early developmental decisions shaping the size and organization of the telencephalon and ii) the role of RNA splicing proteins inside axons and dendrites of developing neurons. In the context of the CNDD, one of the genes the team built a particular interest in is the transcription factor Foxg1 that they identified as the key integrator of signalling input inside the forming telencephalon. The lab’s studies recently demonstrated that Foxg1 expression level dictates the function of the protein (different levels leading to different functions) and unveiled a non-nuclear localisation and role of the protein. The team is now exploring the role of the human and mammalian motifs of this essential forebrain regulator.

Mutations in Foxg1 itself is causing "Foxg1 syndrome" in human and changes in its expression levels is systematically observed in iPSC-derived neurons from ASD patients and thought to be causative to part of ASD developmental dysfunctions. Our contributions will be to understand the molecular mechanism driving Foxg1-dependent integration of fate specification and neurogenesis and the nature and temporal dynamics of its dysregulation in micro/macro-cephaly (including Foxg1 syndrome) and severe ASD, using the zebrafish as well as murine and human cellular models. The Houart team is also expert in genome editing in zebrafish and will support genome editing effort across teams inside the Centre.

Selected publications

Johansson M, Giger FA, Fielding T, Houart C (2019) Dkk1 Controls Cell-Cell Interaction through Regulation of Non-nuclear Beta-Catenin Pools. Dev Cell 51: 775-786.e3
Furlan G, Cuccioli V, Vuillemin N, Dirian L, Muntasell AJ, Coolen M, Dray N, Bedu S, Houart C, Beaurepaire E, Foucher I, Bally-Cuif L (2017) Life-Long Neurogenic Activity of Individual Neural Stem Cells and Continuous Growth Establish an Outside-In Architecture in the Teleost Pallium. Curr Biol 27: 3288-3301.e3

Bielen H, Pal S, Tole S, Houart C (2017) Temporal variations in early developmental decisions: an engine of forebrain evolution. Curr Opin Neurobiol 42: 152-159
Bielen H, Houart C (2014) The Wnt cries many: Wnt regulation of neurogenesis through tissue patterning, proliferation, and asymmetric cell division. Dev Neurobiol 74: 772-80
Dirian L, Galant S, Coolen M, Chen W, Bedu S, Houart C, Bally-Cuif L, Foucher I (2014) Spatial regionalization and heterochrony in the formation of adult pallial neural stem cells. Dev Cell 30: 123-36
Sylvester JB, Rich CA, Yi C, Peres JN, Houart C, Streelman JT (2013) Competing signals drive telencephalon diversity. Nat Commun 4: 1745
Lleras-Forero L, Tambalo M, Christophorou N, Chambers D, Houart C, Streit A (2013) Neuropeptides: developmental signals in placode progenitor formation. Dev Cell 26: 195-203
Lee YB, Chen HJ, Peres JN, Gomez-Deza J, Attig J, Stalekar M, Troakes C, Nishimura AL, Scotter EL, Vance C, Adachi Y, Sardone V, Miller JW, Smith BN, Gallo JM, Ule J, Hirth F, Rogelj B, Houart C, Shaw CE (2013) Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic. Cell Rep 5: 1178-86
Danesin C, Houart C (2012) A Fox stops the Wnt: implications for forebrain development and diseases. Curr Opin Genet Dev 22: 323-30
Bielen H, Houart C (2012) BMP signaling protects telencephalic fate by repressing eye identity and its Cxcr4-dependent morphogenesis. Dev Cell 23: 812-22
Fassier C, Hutt JA, Scholpp S, Lumsden A, Giros B, Nothias F, Schneider-Maunoury S, Houart C, Hazan J (2010) Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway. Nat Neurosci 13: 1380-7
Danesin C, Peres JN, Johansson M, Snowden V, Cording A, Papalopulu N, Houart C (2009) Integration of telencephalic Wnt and hedgehog signaling center activities by Foxg1. Dev Cell 16: 576-87
Caneparo L, Huang YL, Staudt N, Tada M, Ahrendt R, Kazanskaya O, Niehrs C, Houart C (2007) Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek. Genes Dev 21: 465-80