Neural Development – Development of Dorsal Midline Central Nervous System Structures


The Millen Lab is actively studying development of the cerebellar rhombic lip and telencephalic cortical hem represent two dorsal medial germinal zones of the vertebrate CNS which give rise to a numerous important cellular populations. The cerebellar rhombic lip gives rise to several brainstem nuclei and the glutamatergic neurons of the cerebellum. The telencephalic cortical hem is a major source of Cajal Retzius cells and is a transient signaling center required for hippocampal induction. In addition to producing the large diversity of neurons, both zones also generate the choroid plexus epithelium – the source of cerebral spinal fluid and a major blood brain barrier. Disruption of these zones contributes to hydrocephalus and congenital malformations of the cerebellum and cerebral cortex. Despite their importance to basic and clinical neuroscience, little is known about the regulation of the cell fate specification of their derivatives. This is in contrast to CNS ventricular zones which have been extensively studied. Recently the Millen Lab determined that Lmx1a, a LIM-homeodomain transcription factor, is a major regulator of neurogenesis within dorsal medial germinal zones in the CNS. We have shown that Lmx1a is required for the proper production and location of lineages arising from the cerebellar rhombic lip and telencephalic cortical hem. These results provide the first evidence that neurogenesis is heterogeneous within each zone, yet these diverse zones share molecular regulatory mechanisms. The Millen lab is currently using Lmx1a as an entry point to define the molecular and developmental pathways which confer cell fates within the cerebellar rhombic lip and telencephalic cortical hem.