Abstract
Unconventional collagens are nonfribrillar proteins that not only contribute to the structure of extracellular matrices but exhibit unique bio-activities. Although roles for unconventional collagens have been well-established in the development and function of non-neural tissues, only recently have studies identified roles for these proteins in brain development, and more specifically, in the formation and refinement of synaptic connections between neurons. Still, our understanding of the full cohort of unconventional collagens that are generated in the mammalian brain remains unclear. Here, we sought to address this gap by assessing the expression of transmembrane collagens (i.e., collagens XIII, XVII, XXIII and XXV) in mouse brain. Using quantitative PCR and in situ hybridization (ISH), we demonstrate both region- and cell-specific expression of these unique collagens in the developing brain. For the two most highly expressed transmembrane collagens (i.e., collagen XXIII and XXV), we demonstrate that they are expressed by select subsets of neurons in different parts of the brain. For example, collagen XXIII is selectively expressed by excitatory neurons in the mitral/tufted cell layer of the accessory olfactory bulb (AOB) and by cells in the inner nuclear layer (INL) of the retina. On the other hand, collagen XXV, which is more broadly expressed, is generated by subsets of excitatory neurons in the dorsal thalamus and midbrain and by inhibitory neurons in the retina, ventral thalamus and telencephalon. Not only is col25a1 expression present in retina, it appears specifically enriched in retino-recipient nuclei within the brain (including the suprachiasmatic nucleus (SCN), lateral geniculate complex, olivary pretectal nucleus (OPN) and superior colliculus). Taken together, the distinct region- and cell-specific expression patterns of transmembrane collagens suggest that this family of unconventional collagens may play unique, yet-to-be identified roles in brain development and function.
Highlights
Collagens are triple helical extracellular matrix (ECM) proteins assembled from three separate polypeptide (α) chains, each of which contains one or more repeating G-X-Y peptide sequences
To assess region-specific expression patterns of col13a1, col17a1, col23a1 and col25a1, at times correlating with neural circuit development and maturation, we performed Quantitative real-time PCR (qPCR) on RNA isolated from several regions of P21 mouse brain
Each MACIT exhibited a unique pattern of mRNA expression in these regions: the highest level of col25a1 was observed in superior colliculus, while the highest levels of col17a1 and col23a1 were observed in thalamus and the retina, respectively (Figure 1A)
Summary
Collagens are triple helical extracellular matrix (ECM) proteins assembled from three separate polypeptide (α) chains, each of which contains one or more repeating G-X-Y peptide sequences (termed collagenous domains). Presynaptic defects and withdrawal of motor nerve terminals from synaptic sites are present in collagen XIII-deficient mice, but the development of these phenotypes is prevented in mice that lack only the ecto-domain shed form of collagen XIII, suggesting that transmembrane collagen XIII may contribute to synaptic adhesion (Härönen et al, 2017). Another MACIT, collagen XXV, is generated by both spinal motor neurons and developing skeletal muscle fibers and its loss impairs intramuscular growth of motor axons and leads to a failure of motor neuron survival (Tanaka et al, 2014). The distinct, regionand cell-specific patterns of MACIT expression in the brain suggests that this family of unconventional collagens may play unique, yet-to-be identified roles in brain development and function
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