Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of from the Embryonic Mid-Hindbrain Region.

Reduced fibroblast growth factor (FGF) signaling from the mid-hindbrain or isthmus organizer (IsO) during early embryonic development results in hypoplasia of the midbrain and cerebellar vermis. We previously reported evidence for reduced expression and FGF signaling in the mid-hindbrain region of embryos heterozygous for , the gene mutated in CHARGE (Coloboma, Heart defects, choanal Atresia, Retarded growth and development, Genitourinary anomalies and Ear defects) syndrome. However, animals only exhibit mild cerebellar vermis anomalies. As homozygous deletion of is embryonic lethal, we conditionally deleted from the early embryonic mid-hindbrain region to identify the function of CHD7 in mid-hindbrain development. Using a combination of high resolution structural MRI and histology, we report striking midbrain and cerebellar vermis hypoplasia in the homozygous conditional mutants. We show that cerebellar vermis hypoplasia is associated with reduced embryonic expression and an expanded roof plate in rhombomere 1 (r1). These findings identify an essential role for in regulating mid-hindbrain development via .