Versatile Roles of the Chromatin Remodeler CHD7 during Brain Development and Disease

Abstract

CHD7 (Chromo-Helicase-DNA binding protein 7) protein is an ATP-dependent chromatin remodeler. Heterozygous mutation of the CHD7 gene causes a severe congenital disease known as CHARGE syndrome. Most CHARGE syndrome patients have brain structural anomalies, implicating an important role of CHD7 during brain development. In this review, we summarize studies dissecting developmental functions of CHD7 in the brain and discuss pathogenic mechanisms behind neurodevelopmental defects caused by mutation of CHD7. As we discussed, CHD7 protein exhibits a remarkably specific and dynamic expression pattern in the brain. Studies in human and animal models have revealed that CHD7 is involved in multiple developmental lineages and processes in the brain. Mechanistically, CHD7 is essential for neural differentiation due to its transcriptional regulation in progenitor cells.

Keywords: CHARGE syndrome; CHD7; brain development; chromatin remodeler; mouse models.

FIGURE 1

The dynamic expression pattern of CHD7 during neurogenesis and oligodendrogenesis. (A) A cartoon shows the expression level of Chd7 transcript during embryonic neurogenesis, based on in situ hybridization data. (B) A cartoon shows the expression level of CHD7 protein in adult neurogenic lineage in hippocampal dentate gyrus, based on immunostaining results. (C) A cartoon shows the increase of CHD7 expression upon differentiation of GNP and OPC, based on immunostaining results. The degree of redness reflects the expression level of Chd7. Arrows show the direction of differentiation. VZ, ventricular zone; SVZ, subventricular zone; IZ, intermediate zone; CP, cortical plate; qNSC, quiescent neural stem cell; aNSC, active NSC; TAP, transit amplifying progenitor; NB, neuroblast; IN, immature neuron; MN, mature neuron; GNP, granule neuron progenitor; CGN, cerebellar granule neuron; OPC, oligodendrocyte precursor cell; OL, oligodendrocyte.