Chd7 plays a critical role in controlling left–right symmetry during zebrafish somitogenesis

Abstract

Somitogenesis is a complex process during early vertebrate development involving interactions between many factors to form a bilateral somite series. A role for chromatin remodelers in somitogenesis has not yet been demonstrated. Here, we investigate the function of chromodomain helicase DNA binding protein 7 (chd7) during zebrafish somitogenesis. We show that Chd7 deficiency leads to asymmetric segmentation of the presomitic mesoderm (PSM), as revealed by expression of the somitogenesis genes, cdx1a, dlc, her7, mespa, and ripply1. Moreover, we show that abrogation of Chd7 results in the loss of asymmetric expression of spaw in the lateral plate mesoderm, which is consistent with more general laterality defects. Based on the observation that insufficient Chd7 leads to left-right asymmetry defects during PSM segmentation, and because CHD7 has been linked to human spinal deformities, we suggest that zebrafish chd7 morphants may be a good in vivo model to examine the pathophysiology of these diseases. Developmental Dynamics 240:2272-2280,

Role of Chd7 in Zebrafish: A Model for CHARGE Syndrome

“…We recently showed by RT-PCR analysis that the morpholino-targeted region exhibited abnormal splicing of chd7 in embryos injected with chd7 SBMO and normal splicing in uninjected and control-MO injected embryos [19]. Embryos injected with the chd7 SBMO exhibited morphological defects similar to those observed in the chd7 -MO morphants (Fig, 2 D).…”

Genetic Aspects of Congenital and Idiopathic Scoliosis

“…Chd7 enables proper symmetric expression of critically important somitogenesis associated genes located downstream from Wnt including her7 , cdx1a , dlc , mespa , and ripply . Zebrafish morpholinos in which CHD7 was knocked down were noted to have tail kinks and a progressively shortened axis [130]. Chd7 plays an important role in somitogenesis as supported by a lack of distinct somite boundary formation and abnormal expression of ephrin B2a , an important segment polarity gene when this gene is knocked down in zebrafish [131].…”

CHARGEd with neural crest defects

“…Anterior-posterior and dorsalventral axes are indicated, cg, cement gland; e, eye shows strong maternal expression and relatively ubiquitous expression throughout early embryogenesis. Later tissue-specific expression is detected in the brain, eyes, otic vesicle, and somites (Asad et al, 2016;Jacobs-McDaniels & Albertson, 2011;Patten et al, 2012). In the mouse, CHD7 expression commences in NC derivatives like the inner ear, the cranial nerves, and the olfactory epithelium (Bosman et al, 2005), and other tissues affected in CHARGE syndrome including the eye, kidney, gonads and the brain.…”