Memo1 Mediated Tiling of Radial Glial Cells Facilitates Cerebral Cortical Development
Naoki Nakagawa, Charlotte Plestant, Keiko Yabuno-Nakagawa, Jingjun Li, Janice Lee, Chu-Wei Huang, Amelia Lee, Oleh Krupa, Aditi Adhikari, Suriya Thompson, Tamille Rhynes, Victoria Arevalo, Jason L. Stein, Zoltán Molnár, Ali Badache, E. S. Anton
Neuron Published:July 02, 2019 DOI:10.1016/j.neuron.2019.05.049
In the mammalian neocortex, formation of distinct neuronal layers is important for precise information processing. During the embryonic brain development, neural progenitor cells not only generate neurons, but also play an important role in the neuronal layer formation. The process sprouted from the neural progenitor cell, termed radial process (Figure 1), is used as “guide” for migrating neurons. Each neural progenitor cell has a single radial process that extends toward the brain surface in a non-overlapping, regularly interspaced manner, therefore functioning as a “scaffolding system” for the neuronal migration and layer formation. However, the molecular and cellular mechanisms for the generation of this scaffolding system is not well understood.
A team of Dr. Naoki Nakagawa at the National Institute of Genetics and Dr. Eva S. Anton at the University of North Carolina School of Medicine identified mediator of cell motility 1 (Memo1) as a key gene for building this scaffolding system and revealed its role in the neuronal layer formation in the mouse neocortex.
By analyzing embryonic brains of Memo1-knockout mice, they found that radial processes of Memo1-deficient neural progenitor cells showed extensive branching and altered spatial distribution. These defects disrupted the scaffolding system of neural progenitor cells and resulted in neuronal misplacement and disorganized layers. These findings demonstrate that Memo1 is important for neural progenitor cells to form the regularly interspaced scaffolding system to organize cortical neurons into distinct neuronal layers (Figure 1).
Figure 1: The scaffolding system of neural progenitor cells and neuronal layer formation
(Top) In the embryonic neocortex, neural progenitor cells are located at the ventricular surface and extend single radial processes toward the brain surface. Radial processes do not overlap with each other and are regularly interspaced. Newborn neurons migrate toward the superficial area by using this regular array of radial process as a “scaffold”, eventually forming the proper neuronal layer.
(Bottom) In the Memo1-knockout mouse neocortex, the absence of Memo1 function in neural progenitor cells causes hyper-branching and irregular distribution of radial processes. These phenotypes generate an aberrant scaffold, leading to perturbed neuronal layer formation.