Doublecortin reinforces microtubules to promote growth cone advance in soft environments.

ABSTRACT: Doublecortin (DCX) is a microtubule (MT)-associated protein in immature neurons. DCX is essential for early brain development,¹ and DCX mutations account for nearly a quarter of all cases of lissencephaly-spectrum brain malformations^2,3 that arise from a neuronal migration failure through the developing cortex.⁴ By analyzing pathogenic DCX missense mutations in non-neuronal cells, we show that disruption of MT binding is central to DCX pathology. In human-induced pluripotent stem cell (hiPSC)-derived cortical i³Neurons, genome edited to express DCX-mEmerald from the endogenous locus, DCX-MT interactions polarize very early during neuron morphogenesis. DCX interacts with MTs through two conserved DCX domains^5,

SUBMITTER: Dema A 

PROVIDER: S-EPMC11740832 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature