Gene Otp’s Role Extends Beyond Brain Development

A gene long known for its influence on early brain development continues to play a crucial role in adulthood, according to researchers from the Weizmann Institute of Science in Israel. This gene, called Orthopedia (Otp), not only contributes to prenatal brain formation but also helps manage stress response and fat storage later in life. The study, published in Endocrinology, explores the gene’s ongoing impact.

An Inactive Period That Never Comes

Otp operates within the cell nucleus and remains vital throughout an individual’s life. Previously, research focused on its role in developing the hypothalamus, the brain area that controls basic functions like hunger and stress. Disruptions to Otp during the early development phase can have profound effects, such as preventing normal stress responses, as seen in earlier studies involving zebrafish.

The team, led by Professor Gil Levkowitz and Professor Alon Chen, wanted to determine whether Otp functions in the adult brain or if its responsibilities ceased after birth. To investigate, they used mice and created a tool that could deactivate Otp in specific adult brain cells, leaving early development unaltered.

Impactful Findings

Findings from the study were telling. Mice that lacked fully functional Otp released excessive stress hormones, including corticosterone, and exhibited depression-like behaviors, such as withdrawal. Moreover, their metabolism suffered, with decreased thyroid hormone levels and cholesterol increases. Despite eating normally and weighing the same as their unchanged counterparts, these mice stored more body fat.

Otp acts like a control center, directing signals from the body and environment to trigger the appropriate hormonal systems. The evolutionary reuse of Otp for different tasks was evident: during development, it helps brain cells develop specific functions, while in adulthood, it manages stress and energy balance.

Implications for Stress and Metabolism

According to Levkowitz, the research suggests that evolution has adapted this genetic tool for diverse functions. Understanding its operation may lead to improved treatments for stress and metabolism. Rather than shutting down systems when they malfunction, targeted adjustments may restore balance.

“The findings suggest that Otp isn’t just for development. It plays a crucial adult role, coordinating stress, thyroid signaling, temperature, body composition, and hunger,” said Dr. Jessica McCarthy, a licensed clinical psychologist.

McCarthy also noted the study’s illustration of interlinked regulatory systems. What appears as a simple behavior might result from intricate brain-body interactions. She advises patients to undergo regular physical exams to detect physiological changes affecting behavior.

Reference: Levkowitz, G., Chen A., et al. (2026). Disruption of the developmental factor Otp in the adult male forebrain reveals its diverse physiological functions. Endocrinology. https://doi.org/10.1210/endocr/bqag029. Contact Newsweek editors on this story: Sirena Bergman and Cristina Diciu.