Planar cell polarity signalling couples cell division and morphogenesis during neurulation

Area of Science:

• Developmental Biology
• Genetics
• Cell Biology

Background:

• Neural tube closure defects (NTDs) affect 1 in 1,000 births, linked to environmental and genetic factors.
• Planar cell polarity (PCP) signaling, involving proteins like Van Gogh-like 2 (Vangl2), is implicated in neurulation by guiding neural progenitor cells.

Purpose of the Study:

• To investigate the role of PCP signaling in zebrafish neurulation.
• To elucidate the mechanism by which PCP signaling influences neural progenitor cell behavior and neural tube formation.

Main Methods:

• Utilized zebrafish models, including trilobite mutants (lacking Vangl2).
• Observed neural progenitor cell polarization and behavior during neurulation.
• Investigated the impact of blocking cell division on neural tube morphogenesis in Vangl2-deficient embryos.

Main Results:

• Demonstrated that non-canonical Wnt/PCP signaling polarizes neural progenitors along the anteroposterior axis during zebrafish neurulation.
• Showed that Vangl2 loss disrupts this polarization, impairs daughter cell re-integration, and causes neural progenitor accumulation and NTDs.
• Found that inhibiting cell division rescues neural tube defects in Vangl2 mutants, despite ongoing convergence and extension issues.

Conclusions:

• PCP signaling is crucial for coupling cell division with morphogenesis during neurulation.
• This study reveals a novel mechanism linking PCP signaling, cell division, and neural tube development.
• Findings suggest a previously unrecognized pathway contributing to NTDs.