Repetitive and perseverative behaviors are common features of a number of neuropsychiatric diseases such as Angelman's syndrome, Tourette's syndrome, obsessive-compulsive disorder, and autism spectrum disorders. The oxytocin system has been linked to the regulation of repetitive behavior in both animal models and humans, but many of its downstream targets have still to be found. We report that the melanin-concentrating hormone (MCH) system is a target of the oxytocin system in regulating one repetitive behavior, marble burying. First we report that nearly 60% of MCH neurons express oxytocin receptors, and demonstrate using rabies mediated tract tracing that MCH neurons receive direct presynaptic input from oxytocin neurons. Then we show that MCH receptor knockout (MCHR1KO) mice and MCH ablated animals display increased marble burying response while central MCH infusion decreases it. Finally, we demonstrate the downstream role of the MCH system on oxytocin mediated marble burying by showing that central infusions of MCH and oxytocin alone or together reduce it while antagonizing the MCH system blocks oxytocin-mediated reduction of this behavior. Our findings reveal a novel role for the MCH system as a mediator of the role of oxytocin in regulating marble-burying behavior in mice.

Repetitive and perseverative behaviors are common features of a number of neuropsychiatric diseases such as Angelman's syndrome, Tourette's syndrome, obsessive-compulsive disorder, and autism spectrum disorders. The oxytocin system has been linked to the regulation of repetitive behavior in both animal models and humans, but many of its downstream targets have still to be found. We report that the melanin-concentrating hormone (MCH) system is a target of the oxytocin system in regulating one repetitive behavior, marble burying. First we report that nearly 60% of MCH neurons express oxytocin receptors, and demonstrate using rabies mediated tract tracing that MCH neurons receive direct presynaptic input from oxytocin neurons. Then we show that MCH receptor knockout (MCHR1KO) mice and MCH ablated animals display increased marble burying response while central MCH infusion decreases it. Finally, we demonstrate the downstream role of the MCH system on oxytocin mediated marble burying by showing that central infusions of MCH and oxytocin alone or together reduce it while antagonizing the MCH system blocks oxytocin-mediated reduction of this behavior. Our findings reveal a novel role for the MCH system as a mediator of the role of oxytocin in regulating marble-burying behavior in mice.

Skeletal stem cells from the suture mesenchyme, which are referred to as suture stem cells (SuSCs), exhibit long-term self-renewal, clonal expansion, and multipotency. These SuSCs reside in the suture midline and serve as the skeletal stem cell population responsible for calvarial development, homeostasis, injury repair, and regeneration. The ability of SuSCs to engraft in injury site to replace the damaged skeleton supports their potential use for stem cell-based therapy. Here, we identified BMPR1A as essential for SuSC self-renewal and SuSC-mediated bone formation. SuSC-specific disruption of Bmpr1a in mice caused precocious differentiation, leading to craniosynostosis initiated at the suture midline, which is the stem cell niche. We found that BMPR1A is a cell surface marker of human SuSCs. Using an ex vivo system, we showed that SuSCs maintained stemness properties for an extended period without losing the osteogenic ability. This study advances our knowledge base of congenital deformity and regenerative medicine mediated by skeletal stem cells.