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    Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways

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    Author
    Alsanie, WF; Penna, V; Schachner, M; Thompson, LH; Parish, CL
    Date
    2017-08-24
    Source Title
    Scientific Reports
    Publisher
    NATURE PUBLISHING GROUP
    University of Melbourne Author/s
    Alsanie, Walaa; Thompson, Lachlan; Parish, Clare; Penna, Vanessa
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Anatomy and Neuroscience
    Metadata
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    Document Type
    Journal Article
    Citations
    Alsanie, W. F., Penna, V., Schachner, M., Thompson, L. H. & Parish, C. L. (2017). Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways. SCIENTIFIC REPORTS, 7 (1), https://doi.org/10.1038/s41598-017-09599-y.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256783
    DOI
    10.1038/s41598-017-09599-y
    Abstract
    Abnormal development of ventral midbrain (VM) dopaminergic (DA) pathways, essential for motor and cognitive function, may underpin a number of neurological disorders and thereby highlight the importance of understanding the birth and connectivity of the associated neurons. While a number of regulators of VM DA neurogenesis are known, processes involved in later developmental events, including terminal differentiation and axon morphogenesis, are less well understood. Recent transcriptional analysis studies of the developing VM identified genes expressed during these stages, including the cell adhesion molecule with homology to L1 (Chl1). Here, we map the temporal and spatial expression of CHL1 and assess functional roles of substrate-bound and soluble-forms of the protein during VM DA development. Results showed early CHL1 in the VM, corresponding with roles in DA progenitor migration and differentiation. Subsequently, we demonstrated roles for CHL1 in both axonal extension and repulsion, selectively of DA neurons, suggestive of a role in guidance towards forebrain targets and away from hindbrain nuclei. In part, CHL1 mediates these roles through homophilic CHL1-CHL1 interactions. Collectively, these findings enhance our knowledge of VM DA pathways development, and may provide new insights into understanding DA developmental conditions such as autism spectrum disorders.

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