Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter
Connective tissue growth factor (CTGF) is a secreted extracellular matrix-associated protein, which play a role in regulating various cellular functions. Although the expression of CTGF has been reported in the cortical subplate, its function is still not clear. Thus, to explore the significance of...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-02-01
|
| Series: | Frontiers in Neuroanatomy |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnana.2019.00016/full |
| _version_ | 1811279940068311040 |
|---|---|
| author | I-Shing Yu Ho-Ching Chang Ko-Chien Chen Yi-Ling Lu Horng-Tzer Shy Chwen-Yu Chen Kuang-Yung Lee Kuang-Yung Lee Li-Jen Lee Li-Jen Lee Li-Jen Lee |
| author_facet | I-Shing Yu Ho-Ching Chang Ko-Chien Chen Yi-Ling Lu Horng-Tzer Shy Chwen-Yu Chen Kuang-Yung Lee Kuang-Yung Lee Li-Jen Lee Li-Jen Lee Li-Jen Lee |
| author_sort | I-Shing Yu |
| collection | DOAJ |
| description | Connective tissue growth factor (CTGF) is a secreted extracellular matrix-associated protein, which play a role in regulating various cellular functions. Although the expression of CTGF has been reported in the cortical subplate, its function is still not clear. Thus, to explore the significance of CTGF in the brain, we created a forebrain-specific Ctgf knockout (FbCtgf KO) mouse model. By crossing Ctgffl/fl mice with Emx1-Cre transgenic mice, in which the expression of Cre is prenatally initiated, the full length Ctgf is removed in the forebrain structures. In young adult (2–3 months old) FbCtgf KO mice, subplate markers such as Nurr1 and Cplx3 are still expressed in the cortical layer VIb; however, the density of the subplate neurons is increased. Interestingly, in these mutants, we found a reduced structural complexity in the subplate neurons. The distribution patterns of neurons and glial cells, examined by immunohistochemistry, are comparable between genotypes in the somatosensory cortex. However, increased densities of mature oligodendrocytes, but not immature ones, were noticed in the external capsule underneath the cortical layer VIb in young adult FbCtgf KO mice. The features of myelinated axons in the external capsule were then examined using electron microscopy. Unexpectedly, the thickness of the myelin sheath was reduced in middle-aged (>12 months old), but not young adult FbCtgf KO mice. Our results suggest a secretory function of the subplate neurons, through the release of CTGF, which regulates the density and dendritic branching of subplate neurons as well as the maturation and function of nearby oligodendrocytes in the white matter. |
| first_indexed | 2024-04-13T01:04:49Z |
| format | Article |
| id | doaj.art-dd8af3732dbc4f38b5f9541a47e6a9a7 |
| institution | Directory Open Access Journal |
| issn | 1662-5129 |
| language | English |
| last_indexed | 2024-04-13T01:04:49Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroanatomy |
| spelling | doaj.art-dd8af3732dbc4f38b5f9541a47e6a9a72022-12-22T03:09:22ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292019-02-011310.3389/fnana.2019.00016442241Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White MatterI-Shing Yu0Ho-Ching Chang1Ko-Chien Chen2Yi-Ling Lu3Horng-Tzer Shy4Chwen-Yu Chen5Kuang-Yung Lee6Kuang-Yung Lee7Li-Jen Lee8Li-Jen Lee9Li-Jen Lee10Laboratory Animal Center, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital, Keelung, TaiwanDepartment of Neurology, Chang Gung Memorial Hospital, Keelung, TaiwanCollege of Medicine, Chang Gung University, Taoyuan, TaiwanGraduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, TaiwanInstitute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, TaiwanNeurobiology and Cognitive Science Center, National Taiwan University, Taipei, TaiwanConnective tissue growth factor (CTGF) is a secreted extracellular matrix-associated protein, which play a role in regulating various cellular functions. Although the expression of CTGF has been reported in the cortical subplate, its function is still not clear. Thus, to explore the significance of CTGF in the brain, we created a forebrain-specific Ctgf knockout (FbCtgf KO) mouse model. By crossing Ctgffl/fl mice with Emx1-Cre transgenic mice, in which the expression of Cre is prenatally initiated, the full length Ctgf is removed in the forebrain structures. In young adult (2–3 months old) FbCtgf KO mice, subplate markers such as Nurr1 and Cplx3 are still expressed in the cortical layer VIb; however, the density of the subplate neurons is increased. Interestingly, in these mutants, we found a reduced structural complexity in the subplate neurons. The distribution patterns of neurons and glial cells, examined by immunohistochemistry, are comparable between genotypes in the somatosensory cortex. However, increased densities of mature oligodendrocytes, but not immature ones, were noticed in the external capsule underneath the cortical layer VIb in young adult FbCtgf KO mice. The features of myelinated axons in the external capsule were then examined using electron microscopy. Unexpectedly, the thickness of the myelin sheath was reduced in middle-aged (>12 months old), but not young adult FbCtgf KO mice. Our results suggest a secretory function of the subplate neurons, through the release of CTGF, which regulates the density and dendritic branching of subplate neurons as well as the maturation and function of nearby oligodendrocytes in the white matter.https://www.frontiersin.org/article/10.3389/fnana.2019.00016/fullCCN2conditional knockoutsubplatecortical neuronglial cellsdendrite |
| spellingShingle | I-Shing Yu Ho-Ching Chang Ko-Chien Chen Yi-Ling Lu Horng-Tzer Shy Chwen-Yu Chen Kuang-Yung Lee Kuang-Yung Lee Li-Jen Lee Li-Jen Lee Li-Jen Lee Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter Frontiers in Neuroanatomy CCN2 conditional knockout subplate cortical neuron glial cells dendrite |
| title | Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter |
| title_full | Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter |
| title_fullStr | Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter |
| title_full_unstemmed | Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter |
| title_short | Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter |
| title_sort | genetic elimination of connective tissue growth factor in the forebrain affects subplate neurons in the cortex and oligodendrocytes in the underlying white matter |
| topic | CCN2 conditional knockout subplate cortical neuron glial cells dendrite |
| url | https://www.frontiersin.org/article/10.3389/fnana.2019.00016/full |
| work_keys_str_mv | AT ishingyu geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT hochingchang geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT kochienchen geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT yilinglu geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT horngtzershy geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT chwenyuchen geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT kuangyunglee geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT kuangyunglee geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT lijenlee geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT lijenlee geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter AT lijenlee geneticeliminationofconnectivetissuegrowthfactorintheforebrainaffectssubplateneuronsinthecortexandoligodendrocytesintheunderlyingwhitematter |