Bsx controls pineal complex development

Abstract

Neuroendocrine cells in the pineal gland release melatonin during the night and, in teleosts, are directly photoreceptive. During development of the pineal complex, a small number of cells migrate leftward away from the pineal anlage to form the parapineal cell cluster, a process that is crucial for asymmetrical development of the bilateral habenular nuclei. Here, we show that, throughout zebrafish embryonic development, the () gene is expressed in all cell types of the pineal complex. We identified Bmp and Noto/Flh as major regulators of expression in the pineal complex. Upon loss of Bsx through the generation of a targeted mutation, embryos fail to form a parapineal organ and develop right-isomerized habenulae. Crucial enzymes in the melatonin biosynthesis pathway are not expressed, suggesting the absence of melatonin from the pineal gland in mutants. Several genes involved in rod-like or cone-like phototransduction are also abnormally expressed, indicating that Bsx has a pivotal role in the differentiation of multiple cell types in the zebrafish pineal complex.

Circadian regulation and molecular role of the Bsx homeobox gene in the adult pineal gland

“…To examine the ontogenetic expression patterns of Bsx , in situ hybridization was performed on coronal brain sections from rats sacrificed at daytime (ZT6) and at nighttime (ZT18) during pre‐ and postnatal stages ranging from E15 to P30 (Figure ). Bsx was detected in the pineal gland at all ages, as reported in other species, but was undetectable in other brain regions present in the same coronal plane. Both developmental age and ZT exerted significant effects on Bsx expression in the pineal gland ( P < .0001) (Figure ).…”

“…Current knowledge establishes a role of Bsx in development of the pineal gland in several vertebrate species; in addition, genome‐wide large‐scale screening efforts suggest rhythmic expression of Bsx in the mature pineal gland of the rat . The present study expands upon this knowledge by exploring persistent ontogenetic expression, cellular localization, regulation, and molecular role of Bsx in the rat pineal gland, as well as anatomical distribution of BSX transcripts in the human pineal gland.…”

“…The brain‐specific homeobox gene ( Bsx ) is expressed in the developing pineal gland at early stages and is essential for proper pineal morphogenesis in mice, frogs ( Xenopus ) and zebrafish . In the postnatal rodent brain, Bsx is specifically expressed in the pineal gland and the hypothalamus .…”

Conserved Genoarchitecture of the Basal Hypothalamus in Zebrafish Embryos

“…The bsx transcription factor is expressed in several domains within the secondary prosencephalon in mouse and zebrafish (Cremona et al, 2004;Schredelseker and Driever, 2018). Here, comparing bsx expression with arxa as a marker for the alar territories, we found that most bsx expression in the ventral forebrain is restricted to the basal plate (Figures 2A-A ,H).…”

“…For all probes which have been described previously, references are given in Supplementary Table S1. Templates for all other probes were PCR amplified from cDNA and subcloned into pCRII-TOPO plasmid (Invitrogen) as has been described before (Schredelseker and Driever, 2018). Primer sequences are shown in Supplementary Table S1.…”