Abstract
Neurodevelopment and mature brain function are spatiotemporally regulated by various cytokines and chemokines. The chemokine-like neuropeptide FAM19A1 is a member of family with sequence similarity 19 (FAM19), which is predominantly expressed in the brain. Its highly conserved amino acid sequence among vertebrates suggests that FAM19A1 may play important physiological roles in neurodevelopment and brain function. Here we used a LacZ reporter gene system to map the expression pattern of the FAM19A1 gene in the mouse brain. The FAM19A1 expression was observed in several brain regions starting during embryonic brain development. As the brain matured, the FAM19A1 expression was detected in the pyramidal cells of cortical layers 2/3 and 5 and in several limbic areas, including the hippocampus and the amygdala. FAM19A1-deficient mice were used to evaluate the physiological contribution of FAM19A1 to various brain functions. In behavior analysis, FAM19A1-deficient mice exhibited several abnormal behaviors, including hyperactive locomotor behavior, long-term memory deficits and fear acquisition failure. These findings provide insight into the potential contributions of FAM19A1 to neurodevelopment and mature brain function.
Highlights
Developmental and physiological processes in the central nervous system (CNS) are tightly regulated by a series of orchestrated gene expressions to promote the formation of dynamic neural circuitries and to execute diverse brain functions[1,2]
Given emerging evidence that abnormal cytokine profiles are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactive disorder (ADHD), it is important to understand the biological functions of these small secretory proteins in the CNS15,16
FAM19A1 LacZ KI mice were generated to investigate the role of FAM19A1 in the brain
Summary
Developmental and physiological processes in the central nervous system (CNS) are tightly regulated by a series of orchestrated gene expressions to promote the formation of dynamic neural circuitries and to execute diverse brain functions[1,2]. In the adult nervous system, cytokines such as leukemia inhibitory factor (LIF) control neurotransmitter and neuropeptide profiles[11,12], whereas interleukin-1 beta (IL-1β) modulates the activity of local neural networks via reconstructing synaptic plasticity and intercellular communication[13,14] Taken together, these findings indicate that the normal development and physiological functions within the CNS depend on the spatiotemporal regulation of several cytokines and chemokines. We conducted behavioral analyses, showing that FAM19A1-deficient mice exhibit locomotor hyperactivity and deficits in long-term memory and fear acquisition These findings suggest that FAM19A1 may be involved in both neurodevelopment and important brain functions
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