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Development. 2017 Oct 1;144(19):3511-3520. doi: 10.1242/dev.148908. Epub 2017 Aug 31.

Afadin orients cell division to position the tubule lumen in developing renal tubules.

Author information

1
Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
2
Department of Pediatrics, University of California, San Francisco, CA, 94158, USA.
3
Department of Anatomy, University of California, San Francisco, CA, 94158, USA.
4
Institute of Cancer Sciences, University of Glasgow and Cancer Research UK Beatson Institute, Glasgow G61 1BD, UK.
5
Department of Cell Biology, University of Texas Southwestern Medical Center.
6
Department of Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA denise.marciano@utsouthwestern.edu.

Abstract

In many types of tubules, continuity of the lumen is paramount to tubular function, yet how tubules generate lumen continuity in vivo is not known. We recently found that the F-actin-binding protein afadin is required for lumen continuity in developing renal tubules, though its mechanism of action remains unknown. Here, we demonstrate that afadin is required for lumen continuity by orienting the mitotic spindle during cell division. Using an in vitro 3D cyst model, we find that afadin localizes to the cell cortex adjacent to the spindle poles and orients the mitotic spindle. In tubules, cell division may be oriented relative to two axes: longitudinal and apical-basal. Unexpectedly, in vivo examination of early-stage developing nephron tubules reveals that cell division is not oriented in the longitudinal (or planar-polarized) axis. However, cell division is oriented perpendicular to the apical-basal axis. Absence of afadin in vivo leads to misorientation of apical-basal cell division in nephron tubules. Together, these results support a model whereby afadin determines lumen placement by directing apical-basal spindle orientation, resulting in a continuous lumen and normal tubule morphogenesis.

KEYWORDS:

Afadin; Kidney development; Lumen; Mouse; Nephron; Polarity; Tubulogenesis

PMID:
28860115
PMCID:
PMC5665479
DOI:
10.1242/dev.148908
[Indexed for MEDLINE]
Free PMC Article

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