title: Neural crest-specific removal of Zfhx1b in mouse leads to a wide range of neurocristopathies reminiscent of Mowat-Wilson syndrome.
abstract: Mowat-Wilson syndrome is a recently delineated autosomal dominant developmental anomaly, whereby heterozygous mutations in the ZFHX1B gene cause mental retardation, delayed motor development, epilepsy and a wide spectrum of clinically heterogeneous features, suggestive of neurocristopathies at the cephalic, cardiac and vagal levels. However, our understanding of the etiology of this condition at the cellular level remains vague. This study presents the Zfhx1b protein expression domain in mouse embryos and correlates this with a novel mouse model involving a conditional mutation in the Zfhx1b gene in neural crest precursor cells. These mutant mice display craniofacial and gastrointestinal malformations that show resemblance to those found in human patients with Mowat-Wilson syndrome. In addition to these clinically recognized alterations, we document developmental defects in the heart, melanoblasts and sympathetic and parasympathetic anlagen. The latter observations in our mouse model for Mowat-Wilson suggest a hitherto unknown role for Zfhx1b in the development of these particular neural crest derivatives, which is a set of observations that should be acknowledged in the clinical management of this genetic disorder.
authors.affiliation: Laboratory of Molecular Biology (Celgen), KULeuven, Herestraat 49,B-3000 Leuven, Belgium. tom.vandeputte@med.kuleuven.be
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Putte
authors.forename: Annick
authors.initials: A
authors.lastname: Francis
authors.forename: Luc
authors.initials: L
authors.lastname: Nelles
authors.forename: Leo A
authors.initials: LA
authors.lastname: van Grunsven
authors.forename: Danny
authors.initials: D
authors.lastname: Huylebroeck
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D000818:Animals; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000378:metabolism; D005260:Female; D017950:Ganglia, Sensory / Q000196:embryology / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000196:embryology / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009432:Neural Crest / Q000002:abnormalities / Q000196:embryology* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012886:Skull / Q000196:embryology / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000196:embryology / Q000378:metabolism; D013577:Syndrome; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2