The chromatin remodeling protein CHD7, mutated in CHARGE syndrome, is necessary for proper craniofacial and tracheal development. Issue 9 (10th July 2014)

• Record Type: Journal Article
• Authors: Sperry, Ethan D.; Hurd, Elizabeth A.; Durham, Mark A.; Reamer, Elyse N.; Stein, Adam B.; Martin, Donna M.
• Is Part Of: Developmental dynamics. Volume 243:Issue 9(2014:Sep.)
• Page Start: 1055
• Page End: 1066
• Publication Date: 2014-07-10
• Subjects: Morphogenesis -- Periodicals; Anatomy -- Periodicals; Anatomie -- Périodiques; Biologie du développement -- Périodiques; 571.833
• DOI: 10.1002/dvdy.24156
• Languages: English
• ISSNs: 1058-8388

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p> <underline>Background:</underline> Heterozygous mutations in the chromatin remodeling gene <italic>CHD7</italic> cause CHARGE syndrome, a developmental disorder with variable craniofacial dysmorphisms and respiratory difficulties. The molecular etiologies of these malformations are not well understood. Homozygous <italic>Chd7</italic> null mice die by E11, whereas <italic>Chd7<sup>Gt/+</sup></italic> heterozygous null mice are a viable and excellent model of CHARGE. We explored skeletal phenotypes in <italic>Chd7<sup>Gt/+</sup></italic> and <italic>Chd7</italic> conditional knockout mice, using <italic>Foxg1‐Cre</italic> to delete <italic>Chd7</italic> (<italic>Foxg1</italic>‐CKO) in the developing eye, ear, nose, pharyngeal pouch, forebrain, and gut and <italic>Wnt1‐Cre</italic> (<italic>Wnt1</italic>‐CKO) to delete <italic>Chd7</italic> in migrating neural crest cells. <underline>Results:</underline><italic>Foxg1</italic>‐CKO mice exhibited postnatal respiratory distress and death, dysplasia of the eye, concha, and frontal bone, hypoplastic maxillary shelves and nasal epithelia, and reduced tracheal rings. <italic>Wnt1‐</italic>CKO mice exhibited frontal and occipital bone dysplasia, hypoplasia of the maxillary shelves and mandible, and cleft palate. In contrast, heterozygous <italic>Chd7<sup>Gt/+</sup></italic> mice had apparently normal skeletal development. <underline>Conclusions:</underline> Conditional deletion of <italic>Chd7</italic> in ectodermal and endodermal derivatives (<italic>Foxg1‐Cre</italic>) or migrating neural crest cells (<italic>Wnt1‐Cre</italic>) results in varied and more severe craniofacial defects than in <italic>Chd7<sup>Gt/+</sup></italic> mice. These studies indicate that CHD7 has an important, dosage‐dependent role in development of several different craniofacial tissues. <italic>Developmental Dynamics 243:1055–1066, 2014</italic>. © 2014 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.</p> </abstract>