AUTHOR=Yu I-Shing , Chang Ho-Ching , Chen Ko-Chien , Lu Yi-Ling , Shy Horng-Tzer , Chen Chwen-Yu , Lee Kuang-Yung , Lee Li-Jen 

TITLE=Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter

JOURNAL=Frontiers in Neuroanatomy

VOLUME=Volume 13 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2019.00016

DOI=10.3389/fnana.2019.00016

ISSN=1662-5129

ABSTRACT=Connective tissue growth factor (CTGF) is a secreted extracellular matrix-associated protein, which plays roles 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 Ctgf fl/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 cortical layer VIb; however, the density of 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 myelin sheath was found reduced in middle-aged (> 12 months old), nut not young adult FbCtgf KO mice. Our results suggest a secretory function of subplate neurons through the release of CTGF that regulates the density and dendritic branching of subplate neurons as well as the maturation and function of nearby oligodendrocytes in the white matters.