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Chromatin remodelling mechanisms in neurodevelopmental disorders

Albert Basson

Albert Basson

Reader in Developmental and Stem Cell Biology

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Overview

Research in the Basson lab is primarily focused on chromatin remodelling factors implicated in neurodevelopmental disorders. They create and use mouse models to study the functions of these factors during brain development and reveal the mechanisms responsible for disorders like autism.

So far, critical roles for CHD7, the factor mutated in CHARGE syndrome, have been identified in controlling development of the cerebellum. They are investigating the function of CHD8, a high confidence autism-associated factor, and other chromatin remodeling factors directly regulated by, or otherwise functionally associated with CHD8, in brain development. These studies aim to provide fundamental insights into the epigenetic mechanisms that underlie ataxia, developmental delay, autism, intellectual disability and executive dysfunction.

Related to this core interest, novel unbiased chromatin conformation capture techniques are employed to identify cell type-specific distal regulatory elements that control and fine-tune the expression of key neurodevelopmental genes in the cerebellum, in order to identify non-coding substrates for neurodevelopmental disorders. Finally, the group are interested in understanding how non-genetic, environmental factors may affect autism risk.

Selected publications

Whittaker DE, Kasah S, Donovan APA, Ellegood J, Riegman KLH, Volk HA, McGonnell I, Lerch JP, Basson MA (2017) Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome. Am J Med Genet C Semin Med Genet 175

Donovan APA, Yu T, Ellegood J, Riegman KLH, de Geus C, van Ravenswaaij-Arts C, Fernandes C, Lerch JP, Basson MA (2017) Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of Chd7 from the Embryonic Mid-Hindbrain Region. Front Neuroanat 11: 86

Donovan AP, Basson MA (2016) The neuroanatomy of autism - a developmental perspective. J Anat
Jones KM, Sari N, Russell JP, Andoniadou CL, Scambler PJ, Basson MA (2015) CHD7 maintains neural stem cell quiescence and prevents premature stem cell depletion in the adult hippocampus. Stem Cells 33: 196-210
Jackson A, Kasah S, Mansour SL, Morrow B, Basson MA (2014) Endoderm-specific deletion of Tbx1 reveals an FGF-independent role for Tbx1 in pharyngeal apparatus morphogenesis. Dev Dyn 243: 1143-51
Basson MA (2014) Epistatic interactions between Chd7 and Fgf8 during cerebellar development: Implications for CHARGE syndrome. Rare Dis 2: e28688
Magnani D, Hasenpusch-Theil K, Benadiba C, Yu T, Basson MA, Price DJ, Lebrand C, Theil T (2014) Gli3 controls corpus callosum formation by positioning midline guideposts during telencephalic patterning. Cereb Cortex 24: 186-98
Yu T, Meiners LC, Danielsen K, Wong MT, Bowler T, Reinberg D, Scambler PJ, van Ravenswaaij-Arts CM, Basson MA (2013) Deregulated FGF and homeotic gene expression underlies cerebellar vermis hypoplasia in CHARGE syndrome. Elife 2: e01305
Chakkalakal JV, Jones KM, Basson MA, Brack AS (2012) The aged niche disrupts muscle stem cell quiescence. Nature 490: 355-60
Economou AD, Ohazama A, Porntaveetus T, Sharpe PT, Kondo S, Basson MA, Gritli-Linde A, Cobourne MT, Green JB (2012) Periodic stripe formation by a Turing mechanism operating at growth zones in the mammalian palate. Nat Genet 44: 348-51
Yu T, Yaguchi Y, Echevarria D, Martinez S, Basson MA (2011) Sprouty genes prevent excessive FGF signalling in multiple cell types throughout development of the cerebellum. Development 138: 2957-68
Shea KL, Xiang W, LaPorta VS, Licht JD, Keller C, Basson MA, Brack AS (2010) Sprouty1 regulates reversible quiescence of a self-renewing adult muscle stem cell pool during regeneration. Cell Stem Cell 6: 117-29
Randall V, McCue K, Roberts C, Kyriakopoulou V, Beddow S, Barrett AN, Vitelli F, Prescott K, Shaw-Smith C, Devriendt K, Bosman E, Steffes G, Steel KP, Simrick S, Basson MA, Illingworth E, Scambler PJ (2009) Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. J Clin Invest 119: 3301-10
Basson MA, Echevarria D, Ahn CP, Sudarov A, Joyner AL, Mason IJ, Martinez S, Martin GR (2008) Specific regions within the embryonic midbrain and cerebellum require different levels of FGF signaling during development. Development