Limits...
Abundant expression of guidance and synaptogenic molecules in the injured spinal cord.

Jacobi A, Schmalz A, Bareyre FM - PLoS ONE (2014)

Bottom Line: To assign the expression of these molecules to distinct populations of interneurons we labeled short and long propriospinal neurons by retrograde tracing and glycinergic neurons using a transgenically expressed fluorescent protein.Overall the expression pattern of guidance and synaptogenic molecules in the cervical spinal cord appeared to be stable over time and was not substantially altered following a midthoracic spinal cord injury.Taken together, our study indicates that many of the guidance and synaptogenic cues that regulate neuronal circuit formation in development are also present in the adult CNS and therefore likely contribute to the remodelling of axonal connections in the injured spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany.

ABSTRACT

Background: Spinal interneurons have emerged as crucial targets of supraspinal input during post-injury axonal remodelling. For example, lesioned corticospinal projections use propriospinal neurons as relay stations to form intraspinal detour circuits that circumvent the lesion site and contribute to functional recovery. While a number of the molecules that determine the formation of neuronal circuits in the developing nervous system have been identified, it is much less understood which of these cues are also expressed in the injured spinal cord and can thus guide growing collaterals and initiate synaptogenesis during circuit remodelling.

Methodology/principal findings: To address this question we characterized the expression profile of a number of guidance and synaptogenic molecules in the cervical spinal cord of healthy and spinal cord-injured mice by in situ hybridization. To assign the expression of these molecules to distinct populations of interneurons we labeled short and long propriospinal neurons by retrograde tracing and glycinergic neurons using a transgenically expressed fluorescent protein. Interestingly, we found that most of the molecules studied including members of slit-, semaphorin-, synCAM-, neuroligin- and ephrin- families as well as their receptors are also present in the adult CNS. While many of these molecules were abundantly expressed in all interneurons examined, some molecules including slits, semaphorin 7a, synCAM4 and neuroligin 1 showed preferential expression in propriospinal interneurons. Overall the expression pattern of guidance and synaptogenic molecules in the cervical spinal cord appeared to be stable over time and was not substantially altered following a midthoracic spinal cord injury.

Conclusions: Taken together, our study indicates that many of the guidance and synaptogenic cues that regulate neuronal circuit formation in development are also present in the adult CNS and therefore likely contribute to the remodelling of axonal connections in the injured spinal cord.

Show MeSH

Related in: MedlinePlus

In Situ hybridization pattern of plexin A2 and plexin C1 in the cortex.In situ hybridization of PlexinA2 in the cortex (A). No signal is detected with the Sema6a sense probe (B). Dotted lines in A represent layer V of the cortex. (C) Confocal image of double-labeled neurons of layer V (retrogradely-labeled CST projection neurons, green; plexin A2, red). In situ hybridization of PlexinC1 in the cortex (D). No signal is detected with the Sema7a sense probes (E). Dotted lines in D represent layer V of the cortex. (F) Confocal picture of double-labeled CST projection neurons identified by retrograde tracing (retrogradely-labeled CST projection neurons, green; plexin C1, red). Scale bars in A,B,D,E: 100 µm; Scale bars in C, F: 50 µm (25 µm in insets).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3921160&req=5

pone-0088449-g004: In Situ hybridization pattern of plexin A2 and plexin C1 in the cortex.In situ hybridization of PlexinA2 in the cortex (A). No signal is detected with the Sema6a sense probe (B). Dotted lines in A represent layer V of the cortex. (C) Confocal image of double-labeled neurons of layer V (retrogradely-labeled CST projection neurons, green; plexin A2, red). In situ hybridization of PlexinC1 in the cortex (D). No signal is detected with the Sema7a sense probes (E). Dotted lines in D represent layer V of the cortex. (F) Confocal picture of double-labeled CST projection neurons identified by retrograde tracing (retrogradely-labeled CST projection neurons, green; plexin C1, red). Scale bars in A,B,D,E: 100 µm; Scale bars in C, F: 50 µm (25 µm in insets).

Mentions: To determine whether corticospinal axons can integrate attractive or repulsive signals from Sema6a or 7a, we detected the mRNA coding for the main receptor of Sema6a, plexinA2, and the receptor for Sema7a, plexinC1 in the mouse cortex by in situ hybridization. Our results show specific expression of plexinA2 in layers II-III and V-VI of the cortex (Fig. 4.A,B and Table 3) and specific expression of plexinC1 in in layers II-III and V (Fig. 4D,E and Table 3) Notably, both plexinA2 and plexinC1 are expressed in retrogradely-labeled CST projection neurons in layer V(plexinA2: 54,0±3,65%; plexinC1: 70,0±2,00%) (Fig. 4C,F).


Abundant expression of guidance and synaptogenic molecules in the injured spinal cord.

Jacobi A, Schmalz A, Bareyre FM - PLoS ONE (2014)

In Situ hybridization pattern of plexin A2 and plexin C1 in the cortex.In situ hybridization of PlexinA2 in the cortex (A). No signal is detected with the Sema6a sense probe (B). Dotted lines in A represent layer V of the cortex. (C) Confocal image of double-labeled neurons of layer V (retrogradely-labeled CST projection neurons, green; plexin A2, red). In situ hybridization of PlexinC1 in the cortex (D). No signal is detected with the Sema7a sense probes (E). Dotted lines in D represent layer V of the cortex. (F) Confocal picture of double-labeled CST projection neurons identified by retrograde tracing (retrogradely-labeled CST projection neurons, green; plexin C1, red). Scale bars in A,B,D,E: 100 µm; Scale bars in C, F: 50 µm (25 µm in insets).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921160&req=5

pone-0088449-g004: In Situ hybridization pattern of plexin A2 and plexin C1 in the cortex.In situ hybridization of PlexinA2 in the cortex (A). No signal is detected with the Sema6a sense probe (B). Dotted lines in A represent layer V of the cortex. (C) Confocal image of double-labeled neurons of layer V (retrogradely-labeled CST projection neurons, green; plexin A2, red). In situ hybridization of PlexinC1 in the cortex (D). No signal is detected with the Sema7a sense probes (E). Dotted lines in D represent layer V of the cortex. (F) Confocal picture of double-labeled CST projection neurons identified by retrograde tracing (retrogradely-labeled CST projection neurons, green; plexin C1, red). Scale bars in A,B,D,E: 100 µm; Scale bars in C, F: 50 µm (25 µm in insets).
Mentions: To determine whether corticospinal axons can integrate attractive or repulsive signals from Sema6a or 7a, we detected the mRNA coding for the main receptor of Sema6a, plexinA2, and the receptor for Sema7a, plexinC1 in the mouse cortex by in situ hybridization. Our results show specific expression of plexinA2 in layers II-III and V-VI of the cortex (Fig. 4.A,B and Table 3) and specific expression of plexinC1 in in layers II-III and V (Fig. 4D,E and Table 3) Notably, both plexinA2 and plexinC1 are expressed in retrogradely-labeled CST projection neurons in layer V(plexinA2: 54,0±3,65%; plexinC1: 70,0±2,00%) (Fig. 4C,F).

Bottom Line: To assign the expression of these molecules to distinct populations of interneurons we labeled short and long propriospinal neurons by retrograde tracing and glycinergic neurons using a transgenically expressed fluorescent protein.Overall the expression pattern of guidance and synaptogenic molecules in the cervical spinal cord appeared to be stable over time and was not substantially altered following a midthoracic spinal cord injury.Taken together, our study indicates that many of the guidance and synaptogenic cues that regulate neuronal circuit formation in development are also present in the adult CNS and therefore likely contribute to the remodelling of axonal connections in the injured spinal cord.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians University Munich, Munich, Germany.

ABSTRACT

Background: Spinal interneurons have emerged as crucial targets of supraspinal input during post-injury axonal remodelling. For example, lesioned corticospinal projections use propriospinal neurons as relay stations to form intraspinal detour circuits that circumvent the lesion site and contribute to functional recovery. While a number of the molecules that determine the formation of neuronal circuits in the developing nervous system have been identified, it is much less understood which of these cues are also expressed in the injured spinal cord and can thus guide growing collaterals and initiate synaptogenesis during circuit remodelling.

Methodology/principal findings: To address this question we characterized the expression profile of a number of guidance and synaptogenic molecules in the cervical spinal cord of healthy and spinal cord-injured mice by in situ hybridization. To assign the expression of these molecules to distinct populations of interneurons we labeled short and long propriospinal neurons by retrograde tracing and glycinergic neurons using a transgenically expressed fluorescent protein. Interestingly, we found that most of the molecules studied including members of slit-, semaphorin-, synCAM-, neuroligin- and ephrin- families as well as their receptors are also present in the adult CNS. While many of these molecules were abundantly expressed in all interneurons examined, some molecules including slits, semaphorin 7a, synCAM4 and neuroligin 1 showed preferential expression in propriospinal interneurons. Overall the expression pattern of guidance and synaptogenic molecules in the cervical spinal cord appeared to be stable over time and was not substantially altered following a midthoracic spinal cord injury.

Conclusions: Taken together, our study indicates that many of the guidance and synaptogenic cues that regulate neuronal circuit formation in development are also present in the adult CNS and therefore likely contribute to the remodelling of axonal connections in the injured spinal cord.

Show MeSH
Related in: MedlinePlus