Arcuate plan of chick midbrain development.

In spinal cord and hindbrain development, neurons are generated as longitudinal cell columns aligned with the ventral and dorsal midlines. For rostral brain, however, the fundamental structure of early neuronal patterning remains poorly understood. We report here that, in the chick embryo, the ventral midbrain is remarkably regular in its cellular and molecular organization; it is arranged as a reiterative series of arcuate territories arrayed bilateral to the ventral midline. In the mantle layer of the ventral midbrain, an arcuate series of neuronal cell columns (midbrain arcs) is demonstrated by acetylcholinesterase histochemistry and gene expression for class III beta-tubulin, homeodomain transcription factors, and neurotransmitter synthetic enzymes. In the ventricular layer of midbrain progenitor cells, WNT and NOTCH ligand gene expression displays arcuate periodicities that form a tight three-dimensional registration with the arcs of the underlying mantle layer. Ventral midbrain arcuate patterning is even macroscopically visible, forming ridges along the ventricular surface. These observations establish that a single plan of arcuate organization governs the morphogenesis and cell-type specification of the ventral midbrain. Arcs are not restricted to the midbrain tegmentum but extend through the subthalamic tegmentum of the forebrain. Thus, the chick rostral brain, which is classically divided into midbrain and forebrain, can also be partitioned into the following: (1) a neuraxial region of arcs and (2) an anterodorsal cap that includes midbrain tectum and nonsubthalamic forebrain. We show that this partition of brain tissue is supported by the expression patterns of homologs of Drosophila gap genes.