Abnormal laminar position and dendrite development of interneurons in the reeler forebrain.
The majority of cortical and hippocampal interneurons originate in the subcortical telencephalon and migrate tangentially into pallial regions before settling in various cortical layers. The molecular cues that regulate final positioning of specific interneurons in cortical structures have not yet been identified. The positioning of radially migrating principal neurons of the cortex and hippocampus depends upon Reelin, an extracellular protein expressed near the pial surface during embryonic development that is absent in reeler mutant mice. To determine whether the layer specification of interneurons, like that of principal neurons, requires Reelin, we crossed reeler with transgenic mice that contain Green Fluorescent Protein (GFP)-expressing Inhibitory Neurons (GINs). These neurons express basal forebrain markers Dlx1/2 in normal and reeler mice. In normal mice, GINs express Reelin and are localized to specific layers of the cortex and hippocampus. In reeler mutant mice, we show that GINs migrate normally into the pallium, but fail to acquire proper layer position. Double labeling experiments indicate that the neurochemical profile of these interneurons is not generally altered in reeler mice. However, the extension of their cellular processes is abnormal. Quantitative analysis of GINs in the cortex revealed that they are hypertrophic, bearing longer neuritic branches than normal. Thus, the lack of Reelin signaling results in abnormal positioning and altered morphology of forebrain interneurons.
Yabut
Odessa
O
The Cain Foundation Laboratories, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Renfro
Amy
A
Niu
Sanyong
S
Swann
John W
JW
Marín
Oscar
O
D'Arcangelo
Gabriella
G
D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000502:physiology; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology; D003712:Dendrites / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism; D007395:Interneurons / Q000166:cytology*; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000033:anatomy & histology*; D008822:Mice, Transgenic; D016548:Prosencephalon / Q000002:abnormalities* / Q000166:cytology*; D000091042:Reelin Protein; D014157:Transcription Factors / Q000378:metabolism
C088334:Distal-less homeobox proteins; D018398:Homeodomain Proteins; D000091042:Reelin Protein; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C000717128:Reln protein, mouse