{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BSX, a highly conserved brain‐specific homeobox transcription factor, plays a critical role in both the development and function of neural circuits that regulate feeding behavior and energy homeostasis. In mammals, BSX is prominently expressed in hypothalamic regions (for example, in the arcuate nucleus) and the pineal gland, where it functions to up‐regulate the expression of orexigenic neuropeptides such as neuropeptide Y (NPY) and agouti‐related peptide (AgRP)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n By integrating metabolic cues—such as fasting‐induced glucocorticoid signaling—with the transcriptional machinery, BSX promotes AgRP gene expression via interactions with transcription factors like Sp1, CREB, and forkhead box O1, while its own expression is subject to negative regulation by REST binding to neuron‐restrictive silencer elements (NRSE)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its established role in appetite regulation, BSX is also implicated in the modulation of locomotor behavior, thereby contributing to overall energy balance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, its early embryonic expression and conserved function—from Drosophila (where the homolog, bsh, is expressed exclusively in the brain) to vertebrates—underscore a pivotal role in brain development, particularly in the differentiation of regions such as the epiphysis and hypothalamus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Comparable roles for BSX have been observed in non‐mammalian species, including fish, where its expression in hypothalamic nuclei is associated with the central regulation of feeding through modulation of orexigenic and anorexigenic peptides."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n Collectively, these findings establish BSX as an essential molecular mediator that links neuronal metabolic status with the transcriptional control of key neuropeptides, thereby governing both developmental processes and adult behaviors related to energy homeostasis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Su Gao, Guangjing Zhu, Xuefei Gao, et al. 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