The expression of Unc5 homologs and their co-receptors in the postnatal cerebellum [electronic resource].

9781267855817

1 online resource (105 p.)

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The cerebellum plays a central role in motor coordination, balance, and motor learning. The developmental processes leading to the formation of this complex neural network have been studied for decades. However, much of what is known about cerebellum development is limited to descriptive accounts of cellular differentiation and migration; detailed insight to the molecular regulation of these processes is just beginning. While netrin receptors have been previously implicated in cerebellum development, little is known about how this family of guidance receptors contributes to the development of particular neuron types and the establishment of cellular circuitry within the cerebellum. This study shows that the two repulsive netrin receptors Unc5b and Unc5c are up-regulated in migrating granule neurons, suggesting that these proteins may play a role in regulating granule cell development. I provide further evidence that granule cell repulsion to netrin-1 can occur independently of DCC function. Additionally neogenin is abundantly expressed in migrating granule neurons, suggesting that neogenin may substitute for DCC in this cell population to mediate repulsive signaling to netrin. In addition to Neogenin, the IgDCC family member NOPE is also expressed in the external granule cell layer, although further work is needed to characterize the localization of NOPE protein in the developing cerebellum. This study also highlights a putative role for Unc5d in the development of Purkinje neuron dendrites since Unc5d protein expression is abundant in developing Purkinje neuron dendritic arbors and is enriched in synaptic membrane fractions. While Unc5 receptors are typically thought of as axon guidance factors, this evidence is the first to suggest that Unc5 receptors may be involved in dendrite development in vertebrates. Altogether these data highlight distinct roles for the individual Unc5 homologs and their respective co-receptors in the development of granule neurons and Purkinje neurons to contribute to the proper formation of the postnatal cerebellum.

Books / Online / Dissertations & Theses

English

July 24, 2014

Thesis (Ph.D.)--Yale University, 2012.

Yale University. Molecular, Cellular, and Developmental Biology.