Genetic ablation of the Bsx homeodomain transcription factor in zebrafish: Impact on mature pineal gland morphology and circadian behavior

Abstract

The pineal gland is a neuroendocrine structure in the brain, which produces and secretes the hormone melatonin at nighttime and is considered a key element in the circadian clock system. Early morphogenesis of the gland is controlled by a number of transcription factors, some of which remain active in adult life. One of these is the brain-specific homeobox (Bsx), a highly conserved homeodomain transcription factor with a developmental role in the pineal gland of several species, including zebrafish, and regulatory roles in mature pinealocytes of the rat. To determine the role of Bsx in circadian

CYP1B1: A Novel Molecular Biomarker Predicts Molecular Subtype, Tumor Microenvironment, and Immune Response in 33 Cancers

“…The melatonin is further metabolized into 6-hydroxymelatonin (6OH-MEL) by human cytochrome P450 family [ 4 ]. Evidence shows that various biological properties of melatonin, such as the circadian clock [ 5 , 6 , 7 ], sleep regulation [ 8 , 9 ], anti-inflammatory properties [ 10 , 11 , 12 ], immune modulation [ 13 , 14 , 15 ], and anti-cancer activities [ 16 , 17 , 18 ], have been well revealed. Nevertheless, the clinical and immunological function of the cytochrome P450 family in cancer remains unclear.…”

Role of melanocortin system in the locomotor activity rhythms and melatonin secretion as revealed by agouti‐signalling protein (asip1) overexpression in zebrafish

“…In addition, per2 expression has been shown to be higher in the pineal gland than in other regions, 31 as are many accessory clock genes 32 . Pineal‐less mutants also show reduced amplitude in behavioural rhythms, 33 a similar effect to that found after blocking its molecular oscillator (Ben‐Moshe Livne et al 19 see below). However, the presence of photoreceptive peripheral oscillators that can be entrained by light, 34 with a similar molecular structure 35,36 in zebrafish, suggests a distributed circadian system that challenges the notion of a master pineal clock at least in this species.…”

Homeobox gene‐encoded transcription factors in development and mature circadian function of the rodent pineal gland

“…70 Furthermore, targeted mutation or knockdown of bsx prevents the development of the pineal complex in zebrafish larvae 71,72 ; adult bsx mutants are viable, but as a consequence of the lacking pineal gland, they display reduced circadian rhythm amplitude. 73 These findings suggest that Bsx has a highly conserved role in pineal morphogenesis across species. Along this line, gene ontology analyses of RNA sequencing results following the knockdown of Bsx in mature rat pinealocytes revealed a significant overrepresentation of developmental processes among functions of differentially expressed genes, 46 thus further supporting an executive developmental regulatory role of pineal Bsx.…”

“…In the Xenopus pineal organ, Bsx seems to control cell proliferation and differentiation as evidenced by knockdown and gain‐of‐function studies 70 . Furthermore, targeted mutation or knockdown of bsx prevents the development of the pineal complex in zebrafish larvae 71,72 ; adult bsx mutants are viable, but as a consequence of the lacking pineal gland, they display reduced circadian rhythm amplitude 73 . These findings suggest that Bsx has a highly conserved role in pineal morphogenesis across species.…”