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Development. 1994 Nov;120(11):3119-30.

Open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord.

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Max-Planck-Institut für Immunobiologie, Freiburg, Germany.


We describe a new mouse mutation, designated open brain (opb), which results in severe defects in the developing neural tube. Homozygous opb embryos exhibited an exencephalic malformation involving the forebrain, midbrain and hindbrain regions. The primary defect of the exencephaly could be traced back to a failure to initiate neural tube closure at the midbrain-forebrain boundary. Severe malformations in the spinal cord and dorsal root ganglia were observed in the thoracic region. The spinal cord of opb mutant embryos exhibited an abnormal circular to oval shape and showed defects in both ventral and dorsal regions. In severely affected spinal cord regions, a dorsalmost region of cells negative for Wnt-3a, Msx-2, Pax-3 and Pax-6 gene expression was detected and dorsal expression of Pax-6 was increased. In ventral regions, the area of Shh and HNF-3 beta expression was enlarged and the future motor neuron horns appeared to be reduced in size. These observations indicate that opb embryos exhibit defects in the specification of cells along the dorsoventral axis of the developing spinal cord. Although small dorsal root ganglia were formed in opb mutants, their metameric organization was lost. In addition, defects in eye development and malformations in the axial skeleton and developing limbs were observed. The implications of these findings are discussed in the context of dorsoventral patterning of the developing neural tube and compared with known mouse mutants exhibiting similar defects.

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