Bsx, short for Brain-specific homeobox, is a highly conserved homeodomain transcription factor. It plays a pivotal role in multiple biological processes. In the hypothalamus, it is involved in regulating the expression of neuropeptides related to appetite and energy balance, and also links feeding with locomotor activity. In the pineal complex, it is essential for its development and the differentiation of multiple cell types within it. Genetic models, especially zebrafish models, are valuable for studying Bsx [1,2,3,5].

In zebrafish, loss-of-function mutations of Bsx lead to significant phenotypes. Embryos fail to form a parapineal organ and develop right-isomerized habenulae. Enzymes in the melatonin biosynthesis pathway are not expressed, and genes involved in phototransduction are abnormally expressed, indicating its crucial role in pineal complex cell differentiation [1]. In adult zebrafish, bsx-/-mutants show a lack of detectable pineal gland structures, pigmentation changes in the pineal window, reduced pineal transcripts, and altered circadian locomotor activity rhythms [4]. In goldfish, fasting affects the brain expression of BSX, suggesting its sensitivity to nutrient status [3]. In rats and mice, Bsx expression in the hypothalamus is regulated by energy-balance signals like leptin and ghrelin [5].

In conclusion, Bsx is essential for the development and function of the pineal complex and for the regulation of feeding-related and locomotor activities in the hypothalamus. Studies using gene-knockout models, particularly in zebrafish, have revealed its specific roles in these biological processes, which may have implications for understanding related physiological and pathological conditions, such as disrupted circadian rhythms and disorders in appetite regulation.

References:

1. Schredelseker, Theresa, Driever, Wolfgang. 2018. Bsx controls pineal complex development. In Development (Cambridge, England), 145, . doi:10.1242/dev.163477. https://pubmed.ncbi.nlm.nih.gov/29945867/

2. Schredelseker, Theresa, Veit, Florian, Dorsky, Richard I, Driever, Wolfgang. 2020. Bsx Is Essential for Differentiation of Multiple Neuromodulatory Cell Populations in the Secondary Prosencephalon. In Frontiers in neuroscience, 14, 525. doi:10.3389/fnins.2020.00525. https://pubmed.ncbi.nlm.nih.gov/32581684/

3. Vinnicombe, Kelsey R T, Volkoff, Helene. 2022. Possible role of transcription factors (BSX, NKX2.1, IRX3 and SIRT1) in the regulation of appetite in goldfish (Carassius auratus). In Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 268, 111189. doi:10.1016/j.cbpa.2022.111189. https://pubmed.ncbi.nlm.nih.gov/35307341/

4. Carstensen, Mikkel Bloss, Medvetzky, Adar, Weinberger, Alon, Gothilf, Yoav, Rath, Martin Fredensborg. 2022. Genetic ablation of the Bsx homeodomain transcription factor in zebrafish: Impact on mature pineal gland morphology and circadian behavior. In Journal of pineal research, 72, e12795. doi:10.1111/jpi.12795. https://pubmed.ncbi.nlm.nih.gov/35249239/

5. Nogueiras, Ruben, López, Miguel, Lage, Ricardo, Diéguez, Carlos, Tschöp, Matthias H. 2008. Bsx, a novel hypothalamic factor linking feeding with locomotor activity, is regulated by energy availability. In Endocrinology, 149, 3009-15. doi:10.1210/en.2007-1684. https://pubmed.ncbi.nlm.nih.gov/18308842/