ABSTRACT
We report the cloning and expression of a novel murine forkhead/winged helix family member--Foxn4--that is expressed during neural development in the retina, the ventral hindbrain and spinal cord and dorsal midbrain. Retinal Foxn4 expression is associated with the zone of proliferating progenitor cells. In the mouse mutant ocular retardation (or(J)), Foxn4 expression in the retina is significantly reduced and terminates prematurely.
Subject(s)
Eye Proteins/genetics , Gene Expression Regulation, Developmental , Retina/embryology , Transcription Factors/genetics , Amino Acid Sequence , Animals , Cell Differentiation , Cell Division , Cloning, Molecular , Eye Proteins/chemistry , Forkhead Transcription Factors , Gene Expression Profiling , In Situ Hybridization , Mesencephalon/embryology , Mesencephalon/metabolism , Mice , Molecular Sequence Data , Mutation , Retina/cytology , Retina/metabolism , Rhombencephalon/embryology , Rhombencephalon/metabolism , Spinal Cord/embryology , Spinal Cord/metabolism , Stem Cells/cytology , Stem Cells/metabolism , Transcription Factors/chemistryABSTRACT
Neuroepithelial precursors in the ventral ventricular zone (VZ) of the spinal cord generate motor neurons (MNs) and interneurons, and then a subset of precursors starts to produce oligodendrocyte progenitors (OLPs). We show that OLPs originate in the ventral-most part of the Pax6-positive VZ, which at earlier times generates somatic (Isl2/Lim3-positive) MNs. In Small eye (Pax6-deficient) mice, the origin of OLPs is shifted dorsally and both OLPs and Isl2/Lim3 MNs are delayed. We suggest that somatic MNs and OLPs are generated sequentially from a common set of MN-OL precursors whose position in the VZ is influenced by Pax6. Neuron-glia fate switching might be a preprogrammed property of these precursors or a response to feedback from newly generated neurons. OLs developed normally in explants of Isl1(-/-) spinal cords, which lack MNs, arguing against feedback control and suggesting that the neuron-glia switch is an intrinsic developmental program in a specific subset of neural precursors.