Abstract
During development of the primary olfactory system, axon targeting is inaccurate and axons inappropriately project within the target layer or overproject into the deeper layers of the olfactory bulb. As a consequence there is considerable apoptosis of primary olfactory neurons during embryonic and postnatal development and axons of the degraded neurons need to be removed. Olfactory ensheathing cells (OECs) are the glia of the primary olfactory nerve and are known to phagocytose axon debris in the adult and postnatal animal. However, it is unclear when phagocytosis by OECs first commences. We investigated the onset of phagocytosis by OECs in the developing mouse olfactory system by utilizing two transgenic reporter lines: OMP-ZsGreen mice which express bright green fluorescent protein in primary olfactory neurons, and S100β-DsRed mice which express red fluorescent protein in OECs. In crosses of these mice, the fate of the degraded axon debris is easily visualized. We found evidence of axon degradation at embryonic day (E)13.5. Phagocytosis of the primary olfactory axon debris by OECs was first detected at E14.5. Phagocytosis of axon debris continued into the postnatal animal during the period when there was extensive mistargeting of olfactory axons. Macrophages were often present in close proximity to OECs but they contributed only a minor role to clearing the axon debris, even after widespread degeneration of olfactory neurons by unilateral bulbectomy and methimazole treatment. These results demonstrate that from early in embryonic development OECs are the primary phagocytic cells of the primary olfactory nerve.
Keywords:
apoptosis; bulbectomy; degeneratio; neuron; olfactory nerve.
© 2014 Wiley Periodicals, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Calcium-Binding Proteins / metabolism
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Cells, Cultured
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Drug Combinations
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Estradiol / adverse effects
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Estradiol / analogs & derivatives
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GAP-43 Protein / metabolism
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology*
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Luminescent Proteins / genetics
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Lysosomal-Associated Membrane Protein 1 / metabolism
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Mice
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Mice, Transgenic
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Microfilament Proteins / metabolism
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Neuroglia / physiology*
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Neuroglia / ultrastructure
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Norethindrone / adverse effects
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Olfactory Bulb / cytology*
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Olfactory Bulb / growth & development
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Olfactory Bulb / injuries*
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Olfactory Marker Protein / genetics
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Olfactory Marker Protein / metabolism
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Olfactory Mucosa / cytology*
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Olfactory Mucosa / metabolism
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Olfactory Pathways / cytology
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Olfactory Pathways / diagnostic imaging
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Olfactory Pathways / growth & development
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Olfactory Pathways / injuries
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Olfactory Pathways / ultrastructure
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Phagocytes / physiology*
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Phagocytes / ultrastructure
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Receptor, Macrophage Colony-Stimulating Factor / genetics
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Receptor, Macrophage Colony-Stimulating Factor / metabolism
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Receptors, Nerve Growth Factor / metabolism
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S100 Calcium Binding Protein beta Subunit / genetics
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S100 Calcium Binding Protein beta Subunit / metabolism
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Testosterone / adverse effects
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Testosterone / analogs & derivatives
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Ultrasonography
Substances
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Aif1 protein, mouse
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Calcium-Binding Proteins
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Drug Combinations
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GAP-43 Protein
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Luminescent Proteins
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Lysosomal-Associated Membrane Protein 1
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Microfilament Proteins
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Olfactory Marker Protein
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Omp protein, mouse
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Receptors, Nerve Growth Factor
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S100 Calcium Binding Protein beta Subunit
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Ngfr protein, mouse
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estradiol, norethisterone, testosterone drug combination
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Testosterone
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Estradiol
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Receptor, Macrophage Colony-Stimulating Factor
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Norethindrone