Abstract
Both Pax1 and Pax9 belong to the important paired box gene family (PAX), which mainly participates in animal development and sclerotome differentiation. To date, the precise molecular mechanism and related signaling pathway of Pax1 remain unclear. In our study, microinjection of morpholino- (MO-) modified antisense oligonucleotides against pax1b induced pectoral fin bud defects. Furthermore, we demonstrate that the phenotypes caused by the knockdown of Pax1b in zebrafish could not be phenocopied by pax9 MO and could not be rescued by either Pax1a or Pax9 overexpression. We further find that Pax1b affects the expression of col2a1, Uncx4.1, Noggin3, and aggrecan, confirming the role of Pax1b in chondrocyte differentiation and bone maturation. Moreover, we identify an interaction between PAX1 and FOXO1 and find that the interaction was enhanced under hypoxia stress. Together, this evidence for cell death caused by pax1b knockdown provides new insight into the role of the Pax protein family in cell fate determination and tissue specification.
Highlights
The Pax protein family, consisting of numerous transcription factors with a paired box domain containing 128 amino acids, plays a central role in embryonic patterning and organ differentiation [1]
We used zebrafish as an animal model to investigate the biological functions of Pax1b and Pax9, demonstrating that pax1b morphants display serious defects in fin buds and the axis which is different than pax9 morphants
We demonstrate for the first time that PAX1 interacts with FOXO1 and that this interaction is strengthened under hypoxia stress
Summary
The Pax protein family, consisting of numerous transcription factors with a paired box domain containing 128 amino acids, plays a central role in embryonic patterning and organ differentiation [1]. Pax and Pax have similar expression patterns and functions. The expression of both chicken PAX1 and PAX9 genes was the strongest in undifferentiated cells of precartilage condensations or at the margins of differentiated cartilages and was absent from cartilage itself [4]. Both induce chondrogenic differentiation in the sclerotome via targeting Nkx3.2 [5]. It has been reported that PAX1 is a candidate gene in vertebral malformations and congenital scoliosis from the study of clinical genetics and the mouse mutant undulated [8, 9]. MO knockdown of either Pax or Pax causes defects in the neural arch and scoliosis and double knockdown revealed that Pax and Pax function synergistically in sclerotome development [10]
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