Defining unique molecular markers of upper motor neurons in MND
Motor neuron disease (MND) is caused by selective degeneration of both upper and lower motor neurons.
This project seeks to identify UMN-specific molecular factors for the first time. This will be achieved by isolating and purifying UMNs using either fluorescent retrograde tracing from the spinal cord and/or fluorescent reporter mouse lines that are selective for UMNs e.g. transgenic Uchl1-EGFP mice.
Lower motor neurons (LMNs), such as spinal motor neurons, are straightforward to anatomically identify given the simple cytoarchitecture of the spinal cord and their expression of selective markers e.g. cholinergic genes. However, upper motor neurons (UMNs) reside in layer V of the motor cortex and are virtually indistinguishable from other pyramidal neurons, as they lack selective or specific cell markers. UMNs are therefore difficult to identify and define which creates a major roadblock in MND research.
UMNs will be isolated using tissue microdissociation and FACS, then analysed for enrichment compared to other cortical neurons and bulk tissue. Once confirmed, RNA will be extracted from purified UMNs and subject to RNAseq for global gene expression, bioinformatic and pathway analyses to uncover molecular factors unique to UMNs. This project should define molecular factors and therefore markers unique to UMNs for the first time
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