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 typical development of the vertebrate forebrain, with a focus on i) the early developmental decisions shaping the size and organisation of the telencephalon and ii) the role of RNA splicing proteins and RNA processing inside axons and dendrites of developing neurons.

In the context of the MRC CNDD, one of the genes the lab have built a particular interest in is the transcription factor Foxg1. Corinne Houart and her team have identified Foxg1 as the key integrator of signalling input inside the forming telencephalon.

Specific mutations in FOXG1 cause FOXG1 syndrome in people and additionally, changes in its expression levels are systematically observed in iPSC-derived neurons from autistic people and thought to be a causative contributor to ASD development pathways. The lab recently made zebrafish models of the FOXG1 syndrome (neurodevelopmental disorder severely affecting children from birth) and demonstrated that most common mutations, previously expected to prevent formation of FOXG1 proteins, lead to production of a short C-terminal protein. The finding made in zebrafish was confirmed in patient iPSC-derived neurons.  The investigation unveiled a non-nuclear localisation and role of the wildtype and mutant protein. The team is also exploring the role of the human and mammalian motifs of this essential forebrain regulator.

The Houart team is now aiming to understand the molecular mechanisms driving non-nuclear Foxg1 functions in normal and diseased brain development, using the zebrafish as well as murine and human cellular models.

The Houart team is expert in genome editing and high-throughput screens in zebrafish and will support these efforts across teams inside the Centre.

Selected publications

Richard Taylor, Fursham Hamid, Triona Fielding, Patricia M. Gordon, Megan Maloney, Eugene V. Makeyev & Corinne Houart (2022)

Prematurely terminated intron-retaining mRNAs invade axons in SFPQ null-driven neurodegeneration and are a hallmark of ALS

Nature Communications

Nikolas Nikolaou, Patricia M. Gordon, Fursham Hamid, Richard Taylor, Joshua Lloyd-Jones, Eugene V. Makeyev, Corinne Houart (2022) Cytoplasmic pool of U1 spliceosome protein SNRNP70 shapes the axonal transcriptome and regulates motor connectivity Current Biology

Staudt N, Giger FA, Fielding T, Hutt JA, Foucher I, Snowden V, Hellich A, Kiecker C, Houart C (2019) Pineal progenitors originate from a non-neural territory limited by FGF signalling. Development 146

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