Multiphoton microscopy was used to create these movies which compare normal (wild type) and mutant (reeler) cortical development. The reeler mouse is a model of severe human intellectual disability. The green cells are Cajal-Retzius neurons that form a layer on the surface of the developing brain. The red cells are sparsely-labeled deep layer cortical neurons (layers 6 and 5) that are migrating towards the Cajal-Retzius neurons. The imaging occurs during embryonic day 15, corresponding to the first trimester of human gestation. For more details please see Ryan O’Dells paper J Neurosci. 2015 Jul 29;35(30):10659-74 PMID 26224852.
There were two important findings derived from the comparison of wildtype and reeler movies: first, the simple leading process of the migrating neuron directly transforms into the branched apical dendrite during the final stage of migration (called translocation). This finding may indicate a mechanistic connection between dendrite initiation and cellular positioning. Second, in reeler cortices, the dendrite either fails to initiate, or becomes unstable soon after initiation. In either case the unifying misbehavior is neurite instability - particularly in the area near the Cajal-Retzius neurons. NOTE: click on “Vimeo” to play movies at full screen.
We are supported by P50AA017823, an NIH funded center for the study of developmental exposure to alcohol.
We are grateful for additional support from a Clark Pediatric Research Award and prior support from a grant NINDS R01NS066071