Abstract
Neurogenesis and functional brain activity require complex associations of inherently programmed secretory elements that are regulated precisely and temporally. Family with sequence similarity 19 A1 (FAM19A1) is a secreted protein primarily expressed in subsets of terminally differentiated neuronal precursor cells and fully mature neurons in specific brain substructures. Several recent studies have demonstrated the importance of FAM19A1 in brain physiology; however, additional information is needed to support its role in neuronal maturation and function. In this study, dendritic spine morphology in Fam19a1-ablated mice and neurite development during in vitro neurogenesis were examined to understand the putative role of FAM19A1 in neural integrity. Adult Fam19a1-deficient mice showed low dendritic spine density and maturity with reduced dendrite complexity compared to wild-type (WT) littermates. To further explore the effect of FAM19A1 on neuronal maturation, the neurite outgrowth pattern in primary neurons was analyzed in vitro with and without FAM19A1. In response to FAM19A1, WT primary neurons showed reduced neurite complexity, whereas Fam19a1-decifient primary neurons exhibited increased neurite arborization, which was reversed by supplementation with recombinant FAM19A1. Together, these findings suggest that FAM19A1 participates in dendritic spine development and neurite arborization.
Highlights
Neurons are the ultimate operators of the central nervous system (CNS) and are designed to execute various CNS-specific functions
Family with sequence similarity 19 A1 (FAM19A1) shows subtype-specific neuronal expression in various brain regions, including the cortical layers and limbic system, and such distinctive expression patterns suggest that FAM19A1 may play major roles in maintaining specific brain functions
To investigate neuronal integrity in Fam19a1-ablated mice compared to WT mice, morphology of dendritic spines in pyramidal neurons of cortical layer 5 (L5), where FAM19A1 expression occurs, were analyzed [24]
Summary
Neurons are the ultimate operators of the central nervous system (CNS) and are designed to execute various CNS-specific functions. To maintain their functional integrity, each step of neuronal development and functional activity is well-regulated. Dendritic spines are postsynaptic structures that act as functional units of neurons for neural communication [3]. Mature neurons are ready to carry out neural activities via dynamic synaptic plasticity. These processes are precisely controlled by numerous extrinsic factors including secretory molecules, and it is important to evaluate their physiological mechanisms to understand neurological disorders such as neurodevelopmental disorders, dementia, and acute traumatic CNS injuries
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