Dataset Information

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

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 more widely to promote orderly progenitor delamination.

SUBMITTER: Tait CM

PROVIDER: S-EPMC7108746 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Tait Christine M CM Chinnaiya Kavitha K Manning Elizabeth E Murtaza Mariyam M Ashton John-Paul JP Furley Nicholas N Hill Chris J CJ Alves C Henrique CH Wijnholds Jan J Erdmann Kai S KS Furley Andrew A Rashbass Penny P Das Raman M RM Storey Kate G KG Placzek Marysia M

PLoS biology 20200309 3

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 c ...[more]

PMID: 32150534

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Project description:Background and purposeHyperintense fluid-signal anterior median fissure and hyperintense foci resembling the central canal are seen on cervical spine axial T2 MR imaging. They may also be associated with a channel-like T2-hyperintense craniocaudad line on sagittal images. We hypothesized that the hyperintense foci and the sagittal line may represent the base of the anterior median fissure.Materials and methodsIn this exploratory study, 358 cervical MR images were analyzed for recording and comparing the incidence/numbers of hyperintense foci, anterior median fissure, and sagittal line as hyperintense foci, anterior median fissure, and sagittal line per patient when present alone or together, both with and without the sagittal line.ResultsHyperintense foci were identified on 238/358 (66.5%) studies; an anterior median fissure, on 218/358 (60.9%). The hyperintense foci/anterior median fissure ratio was 3.7/2.3 (P = .00001). Anterior median fissures were seen alone less commonly than hyperintense foci were seen alone (P = .045). We identified increased anterior median fissure/patient in a hyperintense foci +anterior median fissure group compared with an anterior median fissure-only group (4.0 versus 3.2, P = .05), with similar hyperintense foci/patient in the hyperintense foci+anterior median fissure and hyperintense foci-only groups (5.5 versus 5.8, P = .35), and proportional distribution of both across the hyperintense foci+anterior median fissure subgroups (hyperintense foci/anterior median fissure ratio, 1.3). The sagittal line in 89 (24.9%) patients was associated with increased hyperintense foci and anterior median fissure/patient. Greater correlation of anterior median fissure/patient to sagittal line presence was seen in sagittal line subgroup analysis.ConclusionsThis exploratory analysis found an increased anterior median fissure per patient in conjunction with hyperintense foci presence, a proportional increase of both across the hyperintense foci+anterior median fissure group, and greater correlation of anterior median fissure per patient with the sagittal line. These findings suggest that anterior median fissure and hyperintense foci are structurally related, that hyperintense foci may commonly be the base of the anterior median fissure, and that the sagittal line is a manifestation primarily of an anterior median fissure, occasionally appearing as channels that may simulate the central canal.

Dataset Information

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

Publications

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

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