Details

Autor(en) / Beteiligte

• Voelker, Courtney Christine Joan

Titel

Differential gene expression of cortical layer v pyramidal neuron subpopulations during development

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2006

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• The overall objective of this study was to correlate phenotypic characteristics of layer V pyramidal neurons with their gene expression patterns. Retrograde tracing combined with immunohistochemistry revealed that three neurofilament proteins (SMI-32, N200, and FNP-7) and nuclear Otx1 were specifically expressed in type I-but not type II-layer V pyramidal neurons, while Er81 was expressed in both type I and type II neurons. Co-localization studies with these markers revealed that at least two distinct populations of type I neurons, those that express nuclear Er81 and those that express SMI-32, N200, and Otx1. Investigation of the Otx1-/- cerebral cortex revealed that SMI-32 expressing or N200 expressing neurons were abnormally positioned with aberrant dendritic morphologies and targeting; whereas the Er81-exprsesing neurons were normally positioned within layer V. Developmental studies revealed that Er81 is expressed in the pallial ventricular zone as layer V neurons are generated suggesting that Er81 may play a role in cell fate determination and differentiation. Pilot experiments were conducted to investigate the co-localization of various molecules in distinct classes of layer V pyramidal neurons. In order to identify novel markers expressed in distinct subclasses of layer V pyramidal neurons, a variety of single-cell RNA extraction techniques were investigated and protocols were optimized. By correlating molecular profiles with other aspects of projection neuron phenotype, the studies presented contributed to the further classification of distinct projection neuron phenotypes. This will not only be important for understanding aspects of normal cortical circuitry and its development, but will also be valuable in evaluating cortical pathology.