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

Lei Gao, Zhufeng Yang, Chitkale Hiremath, Susan E. Zimmerman, Blake Long, Paul R. Brakeman, Keith E. Mostov, David M. Bryant, Katherine Luby-Phelps, Denise K. Marciano

Research output: Contribution to journalArticle

8 Scopus citations

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 apicalbasal axis. Absence of afadin in vivo leads to misorientation of apicalbasal 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.

Original languageEnglish (US)
Pages (from-to)3511-3520
Number of pages10
JournalDevelopment (Cambridge)
Volume144
Issue number19
DOIs
StatePublished - Oct 1 2017

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Gao, L., Yang, Z., Hiremath, C., Zimmerman, S. E., Long, B., Brakeman, P. R., Mostov, K. E., Bryant, D. M., Luby-Phelps, K., & Marciano, D. K. (2017). Afadin orients cell division to position the tubule lumen in developing renal tubules. Development (Cambridge), 144(19), 3511-3520. https://doi.org/10.1242/dev.148908