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

## TL;DR

This study shows that the enzyme MBOAT7 is crucial for brain development by maintaining radial glial cell integrity through phosphatidylinositol remodeling.

## Contribution

The study identifies MBOAT7's role in radial glial cell function and neurogenesis via PI(4,5)P2 regulation.

## Key findings

- Mboat7 deficiency causes Golgi apparatus rounding and reduced apical E-cadherin in radial glial cells.
- Reduced PI(4,5)P2 levels in Mboat7-deficient cortex impair neurogenesis and increase apoptosis.
- Pharmacological inhibition of PI(4,5)P2 synthesis reproduces Golgi rounding in radial glial cells.

## Abstract

Phosphatidylinositol (PI) is highly enriched in arachidonic acid, an essential polyunsaturated fatty acid for brain development. This enrichment is mediated by the phospholipid remodeling enzyme lysophospholipid acyltransferase 11 (LPLAT11), also known as membrane-bound O-acyltransferase 7 (MBOAT7), whose deficiency causes microcephaly in both humans and mice. Here, we show that Mboat7 deficiency impairs indirect neurogenesis in the developing neocortex by compromising radial glial cell (RGC) integrity, resulting in fewer layer II–V neurons. Mboat7-deficient RGCs exhibited decreased proliferation, impaired differentiation into intermediate progenitor cells, and increased apoptosis. These defects were preceded by Golgi apparatus rounding, reduced apical E-cadherin expression, and dysregulated apical detachment of RGCs. Moreover, the Mboat7-deficient cortex displayed reduced PI(4,5)P2 levels, and pharmacological inhibition of PI(4,5)P2 synthesis recapitulated the Golgi rounding observed in Mboat7-deficient RGCs. These findings suggest that compromised RGC integrity due to reduced PI(4,5)P2 levels, resulting from decreased arachidonic acid-containing PI, underlies the microcephaly associated with MBOAT7 deficiency.

•Mboat7 deficiency impairs radial glial cell integrity and indirect neurogenesis•Radial glial cells lacking Mboat7 display Golgi apparatus rounding•PI(4,5)P2 levels decline in the Mboat7-deficient cortex at the onset of neurogenesis•Blocking PI(4,5)P2 synthesis recapitulates Golgi rounding in radial glial cells

Mboat7 deficiency impairs radial glial cell integrity and indirect neurogenesis

Radial glial cells lacking Mboat7 display Golgi apparatus rounding

PI(4,5)P2 levels decline in the Mboat7-deficient cortex at the onset of neurogenesis

Blocking PI(4,5)P2 synthesis recapitulates Golgi rounding in radial glial cells

Neuroscience; Developmental neuroscience; Cellular neuroscience