LPLAT11/MBOAT7-driven phosphatidylinositol remodeling ensures radial glial cell integrity in developing neocortex.

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Phosphatidylinositol (PI) enrichment with arachidonic acid is vital for brain development.
• Lysophospholipid acyltransferase 11 (LPLAT11), also known as membrane-bound O-acyltransferase 7 (MBOAT7), mediates this PI enrichment.
• MBOAT7 deficiency is linked to microcephaly in humans and mice.

Purpose of the Study:

• To investigate the role of MBOAT7 in neocortical development and neurogenesis.
• To elucidate the cellular mechanisms underlying microcephaly in MBOAT7-deficient models.

Main Methods:

• Analysis of MBOAT7-deficient mouse models.
• Assessment of radial glial cell (RGC) proliferation, differentiation, and apoptosis.
• Examination of Golgi apparatus morphology and apical E-cadherin expression.
• Measurement of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels.
• Pharmacological manipulation of PI(4,5)P2 synthesis.

Main Results:

• Mboat7 deficiency impairs indirect neurogenesis by compromising RGC integrity.
• Mboat7-deficient RGCs show reduced proliferation, impaired differentiation, and increased apoptosis.
• Defects include Golgi rounding, reduced apical E-cadherin, and dysregulated apical detachment.
• Reduced PI(4,5)P2 levels were observed in Mboat7-deficient cortices.
• Pharmacological inhibition of PI(4,5)P2 mimicked Golgi rounding in RGCs.

Conclusions:

• MBOAT7 deficiency compromises RGC integrity via reduced PI(4,5)P2 levels.
• This compromised integrity, stemming from decreased arachidonic acid-containing PI, underlies MBOAT7 deficiency-associated microcephaly.