Direct non-cell autonomous Pax6 activity regulates eye development in the zebrafish

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Pax6 homeogene expression is critical for eye development.
• Homeoproteins, including Pax6, possess domains facilitating intercellular passage.
• Investigating Pax6's extracellular function is crucial for understanding early development.

Purpose of the Study:

• To investigate the role of intercellular passage of Pax6 in early eye development.
• To determine if Pax6 functions as a signaling molecule beyond its transcriptional role.
• To block extracellular Pax6 activity in developing zebrafish embryos.

Main Methods:

• Developing strategies to block extracellular Pax6 without affecting its intracellular function.
• Injecting one-cell zebrafish embryos with mRNA encoding a secreted anti-Pax6 antibody.
• Injecting Pax6 antibodies into the extracellular milieu of blastula-stage zebrafish embryos.

Main Results:

• Blocking extracellular Pax6 led to 'dissymmetric eyes', 'one eye only', and 'no eye' phenotypes.
• Lens and retina malformations were observed, with lens phenotypes paralleling retinal defects.
• Early eye field asymmetry and Pax6 expression asymmetry strongly correlated with later eye malformations.

Conclusions:

• Pax6 functions not only as a transcription factor but also as a signaling molecule.
• Pax6 exhibits direct non-cell autonomous activity, influencing development from outside the cell.
• This study provides evidence for Pax6's role in intercellular signaling during vertebrate eye formation.