Microtubule-binding Protein MAP1B Regulates Interstitial Axon Branching of Cortical Neurons Via the Tubulin Tyrosination Cycle

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2024 Feb 22

PMID 38388748

Authors

Jakub Ziak

Joelle M Dorskind

Brian Trigg

Sriram Sudarsanam

Xinyu O Jin

Randal A Hand

Alex L Kolodkin

Affiliations

Soon will be listed here.

Abstract

Regulation of directed axon guidance and branching during development is essential for the generation of neuronal networks. However, the molecular mechanisms that underlie interstitial (or collateral) axon branching in the mammalian brain remain unresolved. Here, we investigate interstitial axon branching in vivo using an approach for precise labeling of layer 2/3 callosal projection neurons (CPNs). This method allows for quantitative analysis of axonal morphology at high acuity and also manipulation of gene expression in well-defined temporal windows. We find that the GSK3β serine/threonine kinase promotes interstitial axon branching in layer 2/3 CPNs by releasing MAP1B-mediated inhibition of axon branching. Further, we find that the tubulin tyrosination cycle is a key downstream component of GSK3β/MAP1B signaling. These data suggest a cell-autonomous molecular regulation of cortical neuron axon morphology, in which GSK3β can release a MAP1B-mediated brake on interstitial axon branching upstream of the posttranslational tubulin code.

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