MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• The choroid plexus (ChP) produces cerebrospinal fluid and forms a critical brain barrier.
• ChP development mechanisms, particularly morphogenesis, remain poorly understood.

Purpose of the Study:

• To investigate the role of WNT5A in the morphogenesis and size of the fourth ventricle (4V) choroid plexus in mice.
• To identify upstream regulators of Wnt5a in 4V ChP development.

Main Methods:

• Systemic Wnt5a knockout and overexpression in mice.
• Conditional deletion of Wnt5a in Foxj1-positive epithelial cells.
• Analysis of WNT5A signaling via ROR1 and ROR2 receptors.
• Investigation of MEIS1 binding to the Wnt5a promoter using gain- and loss-of-function studies.

Main Results:

• Epithelial WNT5A is crucial for 4V ChP size and morphogenesis.
• Wnt5a expression is enriched in Foxj1-positive epithelial cells of the 4V ChP.
• WNT5A acts locally at distal villi tips to activate non-canonical WNT signaling.
• MEIS1 transcription factors regulate Wnt5a expression in the 4V ChP epithelium.

Conclusions:

• WNT5A has a dual function in choroid plexus development.
• MEIS transcription factors are identified as upstream regulators of Wnt5a in the 4V ChP epithelium.
• This study elucidates key molecular mechanisms governing 4V ChP development.