Misregulation of cell adhesion molecules in the Ciona neural tube closure mutant bugeye

Area of Science:

• Developmental Biology
• Chordate Embryogenesis
• Molecular Genetics

Background:

• Neural tube closure (NTC) is critical for central nervous system (CNS) development, with errors causing prevalent birth defects.
• T-Type Calcium Channels (Cav3) have a demonstrated role in NTC, suggesting conserved functions across chordates.
• Previous studies identified a Ciona savignyi mutant (bugeye) implicating Cav3 in anterior NTC defects.

Purpose of the Study:

• To investigate a new Cav3 mutant in Ciona robusta.
• To identify molecular mechanisms underlying NTC defects in bugeye mutants.
• To explore the role of cell adhesion molecules in neural tube development.

Main Methods:

• Generated and analyzed a new Cav3 mutant in Ciona robusta.
• Performed RNA sequencing on Ciona savignyi and Ciona robusta bugeye mutants.
• Utilized CRISPR gene editing to disrupt specific cell adhesion molecule genes.

Main Results:

• RNAseq revealed misregulation of cell-cell recognition and adhesion transcripts in bugeye mutants.
• Two specific genes, Selectin and Fibronectin leucine-rich repeat transmembrane, were aberrantly upregulated.
• Disruption of these genes via CRISPR recapitulated the open brain phenotype observed in bugeye mutants.

Conclusions:

• Cav3 function is essential for proper neural tube closure in chordates.
• Aberrant expression of Selectin and Fibronectin leucine-rich repeat transmembrane contributes to NTC defects.
• These molecules likely play a transient role in tissue separation and adhesion during NTC.