The ATP-dependent chromatin remodeling enzyme CHD7 regulates pro-neural gene expression and neurogenesis in the inner ear.

Abstract	Inner ear neurogenesis is positively regulated by the pro-neural bHLH transcription factors Ngn1 and NeuroD, but the factors that act upstream of this regulation are not well understood. Recent evidence in mouse and Drosophila suggests that neural development depends on proper chromatin remodeling, both for maintenance of neural stem cells and for proper neuronal differentiation. Here, we show that CHD7, an ATP-dependent chromatin remodeling enzyme mutated in human CHARGE syndrome, is necessary for proliferation of inner ear neuroblasts and inner ear morphogenesis. Conditional deletion of Chd7 in the developing otocyst using Foxg1-Cre resulted in cochlear hypoplasia and complete absence of the semicircular canals and cristae. Conditional knockout and null otocysts also had reductions in vestibulo-cochlear ganglion size and neuron number in combination with reduced expression of Ngn1, Otx2 and Fgf10, concurrent with expansion of the neural fate suppressor Tbx1 and reduced cellular proliferation. Heterozygosity for Chd7 mutations had no major effects on expression of otic patterning genes or on cell survival, but resulted in decreased proliferation within the neurogenic domain. These data indicate that epigenetic regulation of gene expression by CHD7 must be tightly coordinated for proper development of inner ear neuroblasts.
Authors	Elizabeth A Hurd, Heather K Poucher, Katherine Cheng, Yehoash Raphael, Donna M Martin
Journal	Development (Cambridge, England) (Development) Vol. 137 Issue 18 Pg. 3139-50 (Sep 2010) ISSN: 1477-9129 [Electronic] England
PMID	20736290 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Chd7 protein, mouse DNA-Binding Proteins DNA Helicases CHD7 protein, human
Topics	Animals Cell Proliferation DNA Helicases (genetics, metabolism) DNA-Binding Proteins (deficiency, genetics, metabolism) Ear, Inner (cytology, embryology, enzymology, innervation) Epigenesis, Genetic Female Gene Expression Regulation, Developmental Humans Male Mice Mice, Knockout Neurogenesis

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