Regulatory feedback between VEGF and ERK pathways controls tip-cell expression during sea urchin skeletogenesis

Area of Science:

• Developmental biology
• Evolutionary developmental biology
• Marine biology

Background:

• The sea urchin skeletogenic gene regulatory network (GRN) is similar to the vertebrate vascularization GRN.
• This suggests biomineralization evolved from an ancestral tubulogenesis GRN.
• Vascular endothelial growth factor (VEGF) and extracellular-signal regulated kinase (ERK) pathways are crucial in both systems.

Purpose of the Study:

• To elucidate the regulatory interactions between VEGF and ERK pathways in sea urchin skeletogenesis.
• To compare these interactions with those in vertebrate angiogenesis.
• To understand the co-option of the ancestral tubulogenesis GRN for biomineralization.

Main Methods:

• Investigated the roles of VEGF and ERK signaling in sea urchin skeletal elongation.
• Analyzed gene expression patterns of VEGFR, Ets1/2, and SM50 in skeletogenic cells.
• Compared regulatory mechanisms between sea urchin skeletogenesis and vertebrate angiogenesis.

Main Results:

• A positive-feedback loop was identified: VEGF signaling activates ERK, which upregulates VEGFR expression in skeletogenic cells.
• ERK is essential for the transcription of Ets1/2 and SM50 at skeletal rod tips.
• ERK also regulates SM50 expression, clearing it from cells at the posterior.

Conclusions:

• The study reveals a novel positive-feedback circuitry involving VEGF and ERK in sea urchin skeletogenesis.
• Similarities and differences in VEGF and ERK regulation highlight the co-option of an ancestral tubulogenesis GRN.
• This research provides insights into the evolution of biomineralization from developmental pathways.