Zygotic hypoxia-inducible factor alpha regulates spicule elongation in the sea urchin embryo

• Published in: Developmental biology 2022-04, Vol.484, p.63-74
• Main Authors: Chang, Wei-Lun, Su, Yi-Hsien
• Format: Article
• Language: English
• Subjects: Animals; Embryo, Nonmammalian - metabolism; Gene Expression Regulation, Developmental; HIFα; Hypoxia - metabolism; Mammals - genetics; Morpholinos - genetics; Morpholinos - metabolism; Morpholinos - pharmacology; Primary mesenchyme cells; Sea urchin embryo; Sea Urchins - genetics; Sea Urchins - metabolism; Skeleton; Transcription Factors - genetics; Transcription Factors - metabolism; Vascular Endothelial Growth Factor A - metabolism; VEGF
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2022.02.004

Sea urchin larval skeletons are produced by skeletogenic primary mesenchyme cells (PMCs), which migrate to form two ventrolateral clusters (VLCs) at the sites where biomineralization is initiated. Both PMC migration and biomineralization are controlled by VEGF signals emitted from lateral ectodermal cells. In mammals, VEGF signaling can be activated by hypoxia-inducible factor alpha (HIFα), an oxygen-sensitive transcription factor. Our previous study showed that the sea urchin maternal HIFα is involved in regulating gene expression along the dorsoventral axis. In this study, we discovered that zygotic hifα is expressed in PMCs, and at the late gastrula stage, hifα transcripts display a graded pattern, with stronger signal in the ventral PMCs than in the dorsal PMCs. We further showed that PMCs are hypoxic, which is a condition typically required for HIFα function. In embryos injected with a splice-blocking morpholino against hifα, elongation of the skeleton was impaired, and expression of vegfr-10-Ig (encodes VEGF receptor; VEGFR) was significantly reduced. This morpholino-caused defect could be partially rescued by injection of vegfr-10-Ig mRNA. Expression patterns of transcription factor and biomineralization genes, such as alx1, tbr, msp130, and the sm30 family, were affected when HIFα was knocked down or when VEGF signaling was inhibited. These results suggest that zygotic HIFα acts upstream or in parallel with VEGF signaling to regulate skeletogenic gene expression and participate in spicule elongation. Our study therefore links HIFα with the known role of VEGF signaling in sea urchin biomineralization. [Display omitted] •The sea urchin hifα gene is activated zygotically in PMCs.•PMCs are hypoxic during normal sea urchin embryogenesis.•Zygotic HIFα is involved in spicule elongation in the sea urchin embryo.•Zygotic HIFα acts upstream or in parallel with VEGF signaling to regulate skeletogenic gene expression.