Pax6 and Msx1, two homeobox genes involved in the development of the subcommissural organ

During mouse central nervous system (CNS) development, the homeobox -contai ning genes Pax6 and Msx1, have a spatial and temporal restricted expression in the CNS and craniofacial skeleton. Both genes are highly expressed in t he glial secretory cells that forms the subcommissural organ (SCO), a circu mventricular organ located at the forebrain-midbrain boundary, in the prete ctal dorsal midline neuroepithelium beneath the posterior commissure. Pax6 (Small eye, Sey/Sey) and Msx1 (-/-) null mutants homozygous fall to develop the SCO and a normal posterior commissure. Pineal gland is also absent in Small eye mice. Analysis of Small eye heterozygotes demonstrated specific P ax6 defects in the developing SCO, with an important reduction in the secre tory basal cell processes, in accordance with the dosage effect of Pax6. Al so for Msx1, a gene-dosage effect was found since heterozygous showed a red uced (about one half) SCO. In both mutants, homozygotes and sometimes heter ozygotes develop hydrocephalus. This suggests a causal relationship between the development of the SCO and of the posterior commissure, and between th e absence of a normal SCO and the development of hydrocephalus.