The Role of Frizzled3 in Mouse Neural Development
| dc.contributor.advisor | Kolodkin, Alex L. | en_US |
| dc.contributor.author | Hua, Zhong | en_US |
| dc.contributor.committeeMember | Sockanathan, Shanthini | en_US |
| dc.contributor.committeeMember | Caterina, Michael J. | en_US |
| dc.contributor.committeeMember | Deans, Michael | en_US |
| dc.date.accessioned | 2015-02-11T04:03:40Z | |
| dc.date.available | 2015-02-11T04:03:40Z | |
| dc.date.created | 2014-12 | en_US |
| dc.date.issued | 2014-05-07 | en_US |
| dc.date.submitted | December 2014 | en_US |
| dc.description.abstract | The development of the nervous system requires the spatiotemporal specification of correct numbers and types of neurons and the establishment of precise synaptic connections between neurons and their targets. The latter aspect involves axon growth along stereotypic trajectories guided by extracellular cues. Recently it has been shown that targeted mutation of Frizzled3 (Fz3) leads to axon guidance and growth defects in major fiber tracts in the rostral brain, including the anterior commissure, and the corticothalamic, thalamocortical, and nigrostriatal tracts, yet a systematic examination of the role of Fz3 in the development of the nervous system has not been made. Here we took advantage of various immunohistochemical methods and found that Fz3 is required for the development of multiple fiber tracts in the central nervous system and distinct cranial and spinal motor nerves in the periphery. In the central nervous system, Fz3 loss-of-function results in a nearly complete absence of three early axon tracts in the brain by embryonic day 11.5, axon guidance defects in catecholaminergic and serotonergic neurons in the brain, and pathfinding and central targeting defects in optic tract axons. Although development and target innervation of sensory neurons are largely unaffected in Fz3-/- mice, somatosensory information cannot be conveyed from the spinal cord to the brain due to loss of ascending spinal sensory fibers. In the periphery, loss of Fz3 leads to axon growth defects in the VIIth and XIIth cranial motor nerves, the phrenic nerve, and dorsal motor nerves in the forelimb and hindlimb. As a secondary effect of axon growth defects, affected motor neurons undergo apoptosis two days prior to the normal wave of developmental cell death. In the hindlimb, loss of Fz3 results in abrupt stalling of the dorsal nerve at a precise location in the nerve plexus, which subsequently leads to complete atrophy of muscles within the anterior compartment of the lower limb. Overall, this study reveals a novel aspect of motor axon growth controlled by a central component of the planar cell polarity signaling pathway and represents a comprehensive examination of the role of Fz3 in mouse neural development. | en_US |
| dc.format.mimetype | application/pdf | en_US |
| dc.identifier.uri | http://jhir.library.jhu.edu/handle/1774.2/37145 | |
| dc.language | en | |
| dc.publisher | Johns Hopkins University | |
| dc.subject | planar cell polarity | en_US |
| dc.subject | axon growth and guidance | en_US |
| dc.subject | central nervous system | en_US |
| dc.subject | motor neuron | en_US |
| dc.subject | neural crest | en_US |
| dc.title | The Role of Frizzled3 in Mouse Neural Development | en_US |
| dc.type | Thesis | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Biochemistry, Cellular and Molecular Biology | en_US |
| thesis.degree.discipline | Neuroscience | en_US |
| thesis.degree.grantor | Johns Hopkins University | en_US |
| thesis.degree.grantor | School of Medicine | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | Ph.D. | en_US |
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