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Secretory function in subplate neurons during cortical development.

Kondo S, Al-Hasani H, Hoerder-Suabedissen A, Wang WZ, Molnár Z - Front Neurosci (2015)

Bottom Line: By comparing gene expression between subplate and layer 6, we found that several genes encoding secreted proteins are highly expressed in subplate neurons.One of these secreted proteins, neuroserpin, encoded by the serpini1 gene, is localized to the ER in subplate cells.We propose that subplate might influence cortical circuit formation through a transient secretory function.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, UK.

ABSTRACT
Subplate cells are among the first generated neurons in the mammalian cerebral cortex and have been implicated in the establishment of cortical wiring. In rodents some subplate neurons persist into adulthood. Here we would like to highlight several converging findings which suggest a novel secretory function of subplate neurons during cortical development. Throughout the postnatal period in rodents, subplate neurons have highly developed rough endoplasmic reticulum (ER) and are under an ER stress condition. By comparing gene expression between subplate and layer 6, we found that several genes encoding secreted proteins are highly expressed in subplate neurons. One of these secreted proteins, neuroserpin, encoded by the serpini1 gene, is localized to the ER in subplate cells. We propose that subplate might influence cortical circuit formation through a transient secretory function.

No MeSH data available.


Subplate neurons in P8 mouse brain strongly express neuroserpin. Immunohistochemistry for anti-neuroserpin (A) and anti-KDEL (B) and their correlation (C) in coronal section of P8 mouse. Note, co-localization of neuroserpin and BiP in subplate neurons (arrows, C; cell in D–F). Immunohistochemistry for anti-neuroserpin (D) and anti-KDEL (H) in coronal section of adult mouse. Neither neuroserpin nor BiP is strongly expressed in the adult subplate. Scale bars: 100 μm (A–C, G–I), 10 μm (D–F).
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Figure 3: Subplate neurons in P8 mouse brain strongly express neuroserpin. Immunohistochemistry for anti-neuroserpin (A) and anti-KDEL (B) and their correlation (C) in coronal section of P8 mouse. Note, co-localization of neuroserpin and BiP in subplate neurons (arrows, C; cell in D–F). Immunohistochemistry for anti-neuroserpin (D) and anti-KDEL (H) in coronal section of adult mouse. Neither neuroserpin nor BiP is strongly expressed in the adult subplate. Scale bars: 100 μm (A–C, G–I), 10 μm (D–F).

Mentions: The plasma cell has a well-developed rough ER to be able to synthetise and secret massive amounts of antibodies. Because of their very similar subcellular morphology (Bloom and Fawcett, 1968), we postulate that subplate neurons also a secretory function. To elucidate this possibility we analyzed the gene expression profile for P8 mouse subplate generated from a microarray comparison on subplate and layer 6a tissue samples (Hoerder-Suabedissen et al., 2009, 2013). Comparing gene expression in the subplate with the adjacent layer 6a in somatosensory and visual cortices, we identified 601 probe sets (corresponding to 383 genes and hypothetical genes) that were expressed at a higher (at least 1.5-fold) level in the subplate compared with layer 6 in both comparisons (Hoerder-Suabedissen et al., 2009). Gene ontology (GO) analysis for cellular localization was performed on this list. Table 1 shows some selected examples of genes that encode extracellular proteins and have the highest four expression levels in absolute mRNA volume. Gene expression of these four genes at P7 was confirmed in the GENSAT Database (Supplementary Figure 1). Of these genes, we focussed on the neuron-specific serine protease inhibitor (neuroserpin), which was initially identified as an axonally secreted protein from neuronal cultures of chicken dorsal root ganglia and belongs to a serine protease inhibitor (serpin) gene family (Osterwalder et al., 1996). To analyze the expression pattern of neuroserpin protein in postnatal and adult mouse brain, we performed immunohistochemical analysis (Figure 3). In the P8 mouse brain, neuroserpin was detected in layer 5 pyramidal cells and subplate neurons (Figure 3A) and co-localized with the ER stress marker BiP (Figures 3B–F). The co-localization of neuroserpin and BiP in these neurons suggests that the production and secretion of neuroserpin contributes to the ER stress condition during the postnatal period. In adult, on the other hand, we could not detect neuroserpin expression in subplate neurons. A selected population of pyramidal cells in layer 5 expresses large levels of neuroserpin also in the adult. This is further supported by our layer-specific transcriptomic analysis in the adult (Belgard et al., 2011; Hoerder-Suabedissen et al., 2013). Similarly, BiP was absent from the subplate but present in layer 5 pyramidal cells in adult brains (Figures 3G–I). These results strongly suggest that subplate neurons have a protein secretion function during the postnatal period, but not or much reduced in adulthood.


Secretory function in subplate neurons during cortical development.

Kondo S, Al-Hasani H, Hoerder-Suabedissen A, Wang WZ, Molnár Z - Front Neurosci (2015)

Subplate neurons in P8 mouse brain strongly express neuroserpin. Immunohistochemistry for anti-neuroserpin (A) and anti-KDEL (B) and their correlation (C) in coronal section of P8 mouse. Note, co-localization of neuroserpin and BiP in subplate neurons (arrows, C; cell in D–F). Immunohistochemistry for anti-neuroserpin (D) and anti-KDEL (H) in coronal section of adult mouse. Neither neuroserpin nor BiP is strongly expressed in the adult subplate. Scale bars: 100 μm (A–C, G–I), 10 μm (D–F).
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Related In: Results  -  Collection

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Figure 3: Subplate neurons in P8 mouse brain strongly express neuroserpin. Immunohistochemistry for anti-neuroserpin (A) and anti-KDEL (B) and their correlation (C) in coronal section of P8 mouse. Note, co-localization of neuroserpin and BiP in subplate neurons (arrows, C; cell in D–F). Immunohistochemistry for anti-neuroserpin (D) and anti-KDEL (H) in coronal section of adult mouse. Neither neuroserpin nor BiP is strongly expressed in the adult subplate. Scale bars: 100 μm (A–C, G–I), 10 μm (D–F).
Mentions: The plasma cell has a well-developed rough ER to be able to synthetise and secret massive amounts of antibodies. Because of their very similar subcellular morphology (Bloom and Fawcett, 1968), we postulate that subplate neurons also a secretory function. To elucidate this possibility we analyzed the gene expression profile for P8 mouse subplate generated from a microarray comparison on subplate and layer 6a tissue samples (Hoerder-Suabedissen et al., 2009, 2013). Comparing gene expression in the subplate with the adjacent layer 6a in somatosensory and visual cortices, we identified 601 probe sets (corresponding to 383 genes and hypothetical genes) that were expressed at a higher (at least 1.5-fold) level in the subplate compared with layer 6 in both comparisons (Hoerder-Suabedissen et al., 2009). Gene ontology (GO) analysis for cellular localization was performed on this list. Table 1 shows some selected examples of genes that encode extracellular proteins and have the highest four expression levels in absolute mRNA volume. Gene expression of these four genes at P7 was confirmed in the GENSAT Database (Supplementary Figure 1). Of these genes, we focussed on the neuron-specific serine protease inhibitor (neuroserpin), which was initially identified as an axonally secreted protein from neuronal cultures of chicken dorsal root ganglia and belongs to a serine protease inhibitor (serpin) gene family (Osterwalder et al., 1996). To analyze the expression pattern of neuroserpin protein in postnatal and adult mouse brain, we performed immunohistochemical analysis (Figure 3). In the P8 mouse brain, neuroserpin was detected in layer 5 pyramidal cells and subplate neurons (Figure 3A) and co-localized with the ER stress marker BiP (Figures 3B–F). The co-localization of neuroserpin and BiP in these neurons suggests that the production and secretion of neuroserpin contributes to the ER stress condition during the postnatal period. In adult, on the other hand, we could not detect neuroserpin expression in subplate neurons. A selected population of pyramidal cells in layer 5 expresses large levels of neuroserpin also in the adult. This is further supported by our layer-specific transcriptomic analysis in the adult (Belgard et al., 2011; Hoerder-Suabedissen et al., 2013). Similarly, BiP was absent from the subplate but present in layer 5 pyramidal cells in adult brains (Figures 3G–I). These results strongly suggest that subplate neurons have a protein secretion function during the postnatal period, but not or much reduced in adulthood.

Bottom Line: By comparing gene expression between subplate and layer 6, we found that several genes encoding secreted proteins are highly expressed in subplate neurons.One of these secreted proteins, neuroserpin, encoded by the serpini1 gene, is localized to the ER in subplate cells.We propose that subplate might influence cortical circuit formation through a transient secretory function.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, UK.

ABSTRACT
Subplate cells are among the first generated neurons in the mammalian cerebral cortex and have been implicated in the establishment of cortical wiring. In rodents some subplate neurons persist into adulthood. Here we would like to highlight several converging findings which suggest a novel secretory function of subplate neurons during cortical development. Throughout the postnatal period in rodents, subplate neurons have highly developed rough endoplasmic reticulum (ER) and are under an ER stress condition. By comparing gene expression between subplate and layer 6, we found that several genes encoding secreted proteins are highly expressed in subplate neurons. One of these secreted proteins, neuroserpin, encoded by the serpini1 gene, is localized to the ER in subplate cells. We propose that subplate might influence cortical circuit formation through a transient secretory function.

No MeSH data available.