Journal
JOURNAL OF COMPARATIVE NEUROLOGY
Volume 501, Issue 4, Pages 631-646Publisher
WILEY
DOI: 10.1002/cne.21283
Keywords
axonal guidance; spinal cord regeneration; in situ hybridization; semaphorins; netrin
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Funding
- NICHD NIH HHS [R24 HD050838-03, R24 HD050838-02, R24 HD050838-05, R24 HD050838-01, R24 HD050838, R24 HD050838-04] Funding Source: Medline
- NINDS NIH HHS [R01 NS038537-07, R01 NS038537-03, R01 NS038537-10, R01 NS038537-06, R01 NS038537-05, R01 NS38537, R01 NS038537-01A1, R01 NS038537-02, R01 NS038537-09, R01 NS038537, R01 NS038537-04, R01 NS038537-08] Funding Source: Medline
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R24HD050838] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS038537] Funding Source: NIH RePORTER
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To explore the role of axon guidance molecules during regeneration in the lamprey spinal cord, we examined the expression of mRNAs for semaphorin 3 (Sema3), semaphorin 4 (Sema4), and netrin during regeneration by in situ hybridization. Control lampreys contained netrin-expressing neurons along the length of the spinal cord. After spinal transection, netrin expression was downregulated in neurons close (500 mu m to 10 mm) to the transection at 2 and 4 weeks. A high level of Sema4 expression was found in the neurons of the gray matter and occasionally in the dorsal and the edge cells. Fourteen days after spinal cord transection Sema4 mRNA expression was absent from dorsal and edge cells but was still present in neurons of the gray matter. At 30 days the expression had declined to some extent in neurons and was absent in dorsal and edge cells. In control animals, Sema3 was expressed in neurons of the gray matter and in dorsal and edge cells. Two weeks after transection, Sema3 expression was upregulated near the lesion, but absent in dorsal cells. By 4 weeks a few neurons expressed Sema3 at 20 mm caudal to the transection but no expression was detected 1 mm from the transection. Isolectin I-B-4 labeling for microglia/macrophages showed that the number of Sema3-expressing microglia/macrophages increased dramatically at the injury site over time. The downregulation of netrin and upregulation of Sema3 near the transection suggests a possible role of netrin and semaphorins in restricting axonal regeneration in the injured spinal cord.
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