From developmental blueprint to adult physiological control: expanding roles of Otp in neuroendocrine regulation

Fekete, Csaba (2026) From developmental blueprint to adult physiological control: expanding roles of Otp in neuroendocrine regulation. ENDOCRINOLOGY, 167 (5). ISSN 0013-7227

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Abstract

Understanding how transcription factors integrate developmental programs with adult physiological function remains a central challenge in neuroendocrinology. Orthopedia homeobox (Otp) has long been recognized as an essential developmental regulator of hypothalamic neuroendocrine lineages (1). Over the past several years, however, a series of studies have begun to redefine Otp not merely as a determinant of embryonic neuronal identity, but as a persistent regulator of adult homeostasis. Three recent papers (2-4) collectively demonstrate that Otp plays a critical role in energy balance and broader neuroendocrine regulation, while revealing increasing complexity in its adult functions. The melanocortin system, consisting of proopiomelanocortin (POMC)-derived melanocortin agonist peptides, the endogenous melanocortin antagonist agouti-related peptide (AgRP), and their receptors, melanocortin-3 and melanocortin-4 receptors (MC3R and MC4R), plays a pivotal role in the regulation of food intake and energy expenditure (5). Studies focusing on the melanocortin system linked Otp to the regulation of energy homeostasis (3, 4). These investigations revealed that Otp directs a developmental fate switch between POMC and AgRP neuron identities and additionally controls the sensitivity of melanocortin target neuronal populations by regulating MC4R expression.

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