Comparative studies of CNS development
Professor of Developmental Neurobiology
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.
Thomas-Jinu S, Gordon PM, Fielding T, Taylor R, Smith BN, Snowden V, Blanc E, Vance C, Topp S, Wong CH, Bielen H, Williams KL, McCann EP, Nicholson GA, Pan-Vazquez A, Fox AH, Bond CS, Talbot WS, Blair IP, Shaw CE, Houart C
(2017) Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development. Neuron
Bielen H, Houart C
(2014) The Wnt cries many: Wnt regulation of neurogenesis through tissue patterning, proliferation, and asymmetric cell division. Dev Neurobiol
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