Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal.

PLoS Biology
C. TaitMarysia Placzek

Abstract

In the spinal cord, the central canal forms through a poorly understood process termed dorsal collapse that involves attrition and remodelling of pseudostratified ventricular layer (VL) cells. Here, we use mouse and chick models to show that dorsal ventricular layer (dVL) cells adjacent to dorsal midline Nestin(+) radial glia (dmNes+RG) down-regulate apical polarity proteins, including Crumbs2 (CRB2) and delaminate in a stepwise manner; live imaging shows that as one cell delaminates, the next cell ratchets up, the dmNes+RG endfoot ratchets down, and the process repeats. We show that dmNes+RG secrete a factor that promotes loss of cell polarity and delamination. This activity is mimicked by a secreted variant of Crumbs2 (CRB2S) which is specifically expressed by dmNes+RG. In cultured MDCK cells, CRB2S associates with apical membranes and decreases cell cohesion. Analysis of Crb2F/F/Nestin-Cre+/- mice, and targeted reduction of Crb2/CRB2S in slice cultures reveal essential roles for transmembrane CRB2 (CRB2TM) and CRB2S on VL cells and dmNes+RG, respectively. We propose a model in which a CRB2S-CRB2TM interaction promotes the progressive attrition of the dVL without loss of overall VL integrity. This novel mechanism may operate ...Continue Reading

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Citations

Sep 15, 2020·Frontiers in Neuroscience·Nanda BoonLucie P Pellissier
Aug 28, 2021·Journal of Developmental Biology·Takuma Shinozuka, Shinji Takada

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Methods Mentioned

BETA
delamination
electron microscopy
transmission electron microscopy
PCR
transgenic
dissection
electrophoresis

Software Mentioned

Gatan Digital Micrograph
Zen Blue
Nikon Elements AR
Axiovision
Image
Huygens Professional
SoftWorx

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