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Review
. 2017 Jan;32(1):7-20.
doi: 10.1007/s00467-016-3326-4. Epub 2016 Feb 22.

A Holey Pursuit: Lumen Formation in the Developing Kidney

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Free PMC article
Review

A Holey Pursuit: Lumen Formation in the Developing Kidney

Denise K Marciano. Pediatr Nephrol. .
Free PMC article

Abstract

The formation of polarized epithelial tubules is a hallmark of kidney development. One of the fundamental principles in tubulogenesis is that epithelia coordinate the polarity of individual cells with the surrounding cells and matrix. A central feature in this process is the segregation of membranes into spatially and functionally distinct apical and basolateral domains, and the generation of a luminal space at the apical surface. This review examines our current understanding of the cellular and molecular mechanisms that underlie the establishment of apical-basal polarity and lumen formation in developing renal epithelia, including the roles of cell-cell and cell-matrix interactions and polarity complexes. We highlight growing evidence from animal models, and correlate these findings with models of tubulogenesis from other organ systems, and from in vitro studies.

Keywords: Afadin; Apical–basal polarity; Cadherin; Cap mesenchyme; Kidney development; Lumen; Nephron; Renal vesicle; Tubulogenesis.

Figures

Figure 1
Figure 1
Diverse cellular mechanisms of lumen formation. Mechanisms of budding, wrapping, entrapment, cavitation and hollowing are illustrated. The apical surface (red) and apical cell-cell junctions (green) are shown.
Figure 1
Figure 1
Diverse cellular mechanisms of lumen formation. Mechanisms of budding, wrapping, entrapment, cavitation and hollowing are illustrated. The apical surface (red) and apical cell-cell junctions (green) are shown.
Figure 2
Figure 2
Nephron tubulogenesis and lumen formation. A subset of the metanephric mesenchyme containing nephron progenitors forms a cap around the ureteric bud (UB) epithelium (green with a blue lumen). This mesenchyme, referred to as the cap mesenchyme (gray), condenses to form pretubular aggregates. In pretubular aggregates, pre-apical domains (red) are present in numerous membranes. Pre-apical domains contain the polarity determinant Par3. These domains reorganize and coalesce in an afadin-dependent manner to form 1–2 small apical foci/lumen in primitive renal vesicles. Pre-apical domain constituents are redistributed to apical lateral cell junctions (not illustrated) as the lumen expands in the mature renal vesicle. Next, the expanded lumen (red) extends toward the ureteric bud lumen (blue) in the extended renal vesicle. Additional separate lumens form in the distal segment. These additional distal lumens eventually coalesce. Finally, the extended lumen joins the ureteric bud lumen at the s-shaped body stage, where a pronounced s-shaped lumen is visible. Various nephron stages are depicted as black with red lumens. Reproduced and modified from Yang et al., 2013.
Figure 3
Figure 3. Apical basal polarity in an epithelial cell
(A) Several complexes confer apical basal polarity in epithelia. (a) Integrin complexes generate cell-matrix adhesion and provide spatial cues. (b) Polarity complexes define the apical and basolateral surfaces. The Par complex (Par3, aPKC, Par6, Cdc42) and Crumbs complex (Crb, Pals, PatJ) are apical, and the Scribble complex (Scrib, Dlg, Lgl) is basolateral. The podocalyxin complex (Podxl, Ezrin, NHERF) is also apical. (c) Adherens junction (AJ) and tight junction (TJ) proteins also establish polarity and maintain the barrier between apical and basolateral. (d) Vesicular trafficking complexes (not shown) also generate and maintain polarity. (B) Components of an adherens junction are illustrated. Cadherins and nectins are two major transmembrane receptors, signaling through their adaptor proteins, the catenins and afadin respectively. Catenins include α-catenin, β-catenin, and p120 catenin, as shown. Afadin and α-catenin connect the AJ to the actin cytoskeleton. Afadin interacts with many proteins in addition to nectins, including Rap1, ZO1, and Plekha7 [119].

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