A holey pursuit: lumen formation in the developing kidney

Marciano, Denise K.

doi:10.1007/s00467-016-3326-4

Cited by 29 publications

(23 citation statements)

References 119 publications

(159 reference statements)

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“…Epithelial tubules are one of the most common tissue types in metazoa, and there is remarkable diversity in the structure and mechanisms by which tubules develop (Marciano, 2017;Iruela-Arispe and Beitel, 2013). Despite differences, a key process in tubulogenesis is the development of cell polarity, the segregation of functionally distinct plasma membrane domains.…”

Section: Introductionmentioning

confidence: 99%

Developing renal tubules orient cell division via Afadin to position the tubule lumen

et al. 2017

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In many types of tubules, continuity of the lumen is paramount to tubular function, yet how tubules generate lumen continuity 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 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, 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 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.

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Section: Introductionmentioning

confidence: 99%

Developing renal tubules orient cell division via Afadin to position the tubule lumen

et al. 2017

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“…Epithelial tubules are a component of many organs, including the kidney [1, 2]. A central feature of tubulogenesis is the segregation of spatially and functionally distinct plasma membrane surfaces, called apical-basal polarization, within each cell.…”

Section: Introductionmentioning

confidence: 99%

Role of CD34 family members in lumen formation in the developing kidney

Yang

Zimmerman

Tsunezumi

et al. 2016

Developmental Biology

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Previous studies have shown CD34 family member Podocalyxin is required for epithelial lumen formation in vitro. We demonstrate that Endoglycan, a CD34 family member with homology to Podocalyxin, is produced prior to lumen formation in developing nephrons. Endoglycan localizes to Rab11-containing vesicles in nephron progenitors, and then relocalizes to the apical surface as progenitors epithelialize. Once an apical/luminal surface is formed, Endoglycan (and the actin-binding protein Ezrin) localize to large, intraluminal structures that may be vesicles/exosomes. We generated mice lacking Endoglycan and found mutants had timely initiation of lumen formation and continuous lumens, similar to controls. Mice with conditional deletion of both Endoglycan and Podocalyxin in developing nephrons also had normal tubular lumens. Despite this, Endoglycan/Podocalyxin is required for apical recruitment of the adaptor protein NHERF1, but not Ezrin, in podocyte precursors, a subset of the epithelia. In summary, while CD34 family members appear dispensable for lumen formation, our data identify Endoglycan as a novel pre-luminal marker and suggest lumen formation occurs via vesicular trafficking of apical cargo that includes Endoglycan.

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“…We took a genetic approach to study pancreatic lumen development and its influence on endocrine cell fate. Given the function of the scaffolding molecule Afadin in kidney tubulogenesis, we hypothesized that Afadin may play a similar role during pancreas development (Takai et al 2008;Yang et al 2013;Marciano 2017). We further hypothesized that the Afadin mutant model could be used as a tool to manipulate pancreatic lumens to assess impact on cell fate, including endocrine cells.…”

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confidence: 99%

Afadin and RhoA control pancreatic endocrine mass via lumen morphogenesis

et al. 2017

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Proper lumen morphogenesis during pancreas development is critical to endocrine and exocrine cell fate. Recent studies showed that a central network of lumens (termed core), but not the surrounding terminal branches (termed periphery), produces most islet endocrine cells. To date, it remains unclear how pancreatic lumens form and remodel and which aspects of lumen morphogenesis influence cell fate. Importantly, models testing the function of the central lumen network as an endocrine niche are lacking. Here, we identify mechanisms underlying lumen formation and remodeling and show that central lumen network morphogenesis impacts pancreatic endocrine mass. We show that loss of the scaffolding protein Afadin disrupts de novo lumenogenesis and lumen continuity in the tip epithelium. Codepletion of the actomyosin regulator RhoA and Afadin results in defects in the central lumens and arrests lumen remodeling. This arrest leads to prolonged perdurance of the central lumen network over developmental time and expansion of the endocrine progenitor population and, eventually, endocrine mass. Our study uncovers essential roles of Afadin and RhoA in pancreatic central lumen morphogenesis, which subsequently determines endocrine cell mass.

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A holey pursuit: lumen formation in the developing kidney

Cited by 29 publications

References 119 publications

Developing renal tubules orient cell division via Afadin to position the tubule lumen

Developing renal tubules orient cell division via Afadin to position the tubule lumen

Role of CD34 family members in lumen formation in the developing kidney

Afadin and RhoA control pancreatic endocrine mass via lumen morphogenesis

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