Dorsal patterning defects in the hindbrain, roof plate and skeleton in thedreher (dr(J)) mouse mutant

dreher is a spontaneous mouse mutation in which adult animals display a com plex phenotype associated with hearing loss, neurological, pigmentation and skeletal abnormalities. During early embryogenesis, the neural tube of dre her mutants is abnormally shaped in the region of the rhomboencephalon, due to problems in the formation of a proper roof plate over the otic hindbrai n. We have studied the expression of Hox/lacZ transgenic mouse strains in t he dreher background and shown that primary segmentation of the neural tube is not altered in these mutants, although correct morphogenesis is affecte d resulting in misshapen rhombomeres. Neural crest derivatives from rhombom ere 6, such as the glossopharyngeal ganglion, are defective, and the dorsal neural tube marker Wnt1 is absent from this segment. Selected trunk neural crest populations are also altered, as there is a lack of pigmentation in the thoracic region of mutant mice. Skeletal defects include abnormal crani al bones of neural crest origin, and improper fusion of the dorsal aspects of cervical and thoracic vertebrae. Taken together, the gene affected in th e dreher mutant is responsible for correct patterning of the dorsal-most ce ll types of the neural tube, that is, the neural crest and the roof plate, in the hindbrain region. Axial skeletal defects could reflect inductive inf luence of the dorsal neural tube on proper fusion of the neural arches. It is possible that a common precursor population for both neural crest and ro of plate is the cellular target of the dreher mutation. (C) 2000 Elsevier S cience Ireland Ltd. All rights reserved.