Origin and Fate of Pendrin-Positive Intercalated Cells in Developing Mouse Kidney

Song, Ho Kyung; Kim, Wan Young; Lee, Hyun‐Wook; Park, Eun Young; Han, Ki Hwan; Nielsén, Sören; Madsen, Kirsten; Kim, Jin

doi:10.1681/asn.2006101076

Cited by 23 publications

(19 citation statements)

References 26 publications

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“…Similarly, pendrin-expressing intercalated cells appear in the connecting tubule as early as E14, but appear in the cortical collecting tubule only after birth (29). In medullary collecting tubules, pendrin-positive cells appear during embryonic development but are eliminated after birth by apoptosis.…”

Section: Discussionmentioning

confidence: 98%

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Gao

Eladari

Leviel

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Acid–base transport in the renal collecting tubule is mediated by two canonical cell types: the β-intercalated cell secretes HCO 3 by an apical Cl:HCO 3 named pendrin and a basolateral vacuolar (V)-ATPase. Acid secretion is mediated by the α-intercalated cell, which has an apical V-ATPase and a basolateral Cl:HCO 3 exchanger (kAE1). We previously suggested that the β-cell converts to the α-cell in response to acid feeding, a process that depended on the secretion and deposition of an extracellular matrix protein termed hensin (DMBT1). Here, we show that deletion of hensin from intercalated cells results in the absence of typical α-intercalated cells and the consequent development of complete distal renal tubular acidosis (dRTA). Essentially all of the intercalated cells in the cortex of the mutant mice are canonical β-type cells, with apical pendrin and basolateral or diffuse/bipolar V-ATPase. In the medulla, however, a previously undescribed cell type has been uncovered, which resembles the cortical β-intercalated cell in ultrastructure, but does not express pendrin. Polymerization and deposition of hensin (in response to acidosis) requires the activation of β1 integrin, and deletion of this gene from the intercalated cell caused a phenotype that was identical to the deletion of hensin itself, supporting its critical role in hensin function. Because previous studies suggested that the conversion of β- to α-intercalated cells is a manifestation of terminal differentiation, the present results demonstrate that this differentiation proceeds from HCO 3 secreting to acid secreting phenotypes, a process that requires deposition of hensin in the ECM.

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Section: Discussionmentioning

confidence: 98%

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Gao

Eladari

Leviel

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…In mice, ICs are first observed in the developing medullary CD and connecting tubule, yet are not seen in the cortical CD throughout prenatal development. 20,21 In the immediate postnatal period, the IC distribution shifts from the inner medullary CD to the cortical CD, similar to the adult distribution across several species. 14,[22][23][24][25] The full extent of the effects of obstruction on CD epithelial remodeling and on postnatal CD physiology is unknown.…”

mentioning

confidence: 57%

“…20,35,36 Unlike human nephrogenesis, which is completed in utero, renal development in the rodent continues into the early postnatal period. In the mouse and rat, immature ICs first appear in the medullary CD and connecting tubule early in kidney development (E10.5 to 11.0 days) with type A cells being the first differentiated subtype to appear, and type B and non-A non-B cells emerging near the end of fetal gestation (E21 days).…”

Section: Discussionmentioning

confidence: 99%

“…Of note, ICs are not observed in the rodent cortical CD at any fetal age, and it has been suggested that the ICs of the ureteric bud-derived medullary CD and metanephric mesenchyme-derived connecting tubule may arise independently. 20 In the final stages of rodent nephrogenesis, which occurs postnatally, ICs are observed in the cortical CD and subsequently are lost from the papillary inner medullary CD.…”

Section: Discussionmentioning

confidence: 99%

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Remodeling of the Fetal Collecting Duct Epithelium

Hiatt

Ivanova

Torán

et al. 2010

The American Journal of Pathology

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Congenital urinary tract obstruction induces changes to the renal collecting duct epithelium, including alteration and depletion of intercalated cells. To study the effects of obstruction on the ontogeny of intercalated cell development, we examined normal and obstructed human fetal and postnatal kidneys. In the normal human fetal kidney, intercalated cells originated in the medullary collecting duct at 8 weeks gestation and remained most abundant in the inner medulla throughout gestation. In the cortex, intercalated cells were rare at 18 and 26 weeks gestation and observed at low abundance at 36 weeks gestation. Although early intercalated cells exhibit an immature phenotype, Type A intercalated cells predominated in the inner and outer medullae at 26 and 36 weeks gestation with other intercalated cell subtypes observed rarely. Postnatally, the collecting duct epithelium underwent a remodeling whereby intercalated cells become abundant in the cortex yet absent from the inner medulla. In 18-week obstructed kidneys with mild to moderate injury, the intercalated cells became more abundant and differentiated than the equivalent age-matched normal kidney. In contrast, more severely injured ducts of the late obstructed kidney exhibited a significant reduction in intercalated cells. These studies characterize the normal ontogeny of human intercalated cell development and suggest that obstruction induces premature remodeling and differentiation of the fetal collecting duct epithelium.

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“…Moreover, a developmental series shows that pendrin is already expressed in PSC precursors as they undergo intercalation, with ae1 expression following soon thereafter, suggesting that PSCs differentiate as distinct subtypes (see Fig. S3 in the supplementary material) (see also Song et al, 2007). As these developing PSC subtypes have yet to encounter the external environment, it is unlikely that they are first generated in the skin as generic or mixed subtypes that only resolve into the two polar opposites based on physiological conditions.…”

Section: Incs Subtypes In the Skinmentioning

confidence: 99%

Specification of ion transport cells in theXenopuslarval skin

2011

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SUMMARYSpecialized epithelial cells in the amphibian skin play important roles in ion transport, but how they arise developmentally is largely unknown. Here we show that proton-secreting cells (PSCs) differentiate in the X. laevis larval skin soon after gastrulation, based on the expression of a 'kidney-specific' form of the H + v-ATPase that localizes to the plasma membrane, orthologs of the Cl -/HCO 3 -antiporters ae1 and pendrin, and two isoforms of carbonic anhydrase. Like PSCs in other species, we show that the expression of these genes is likely to be driven by an ortholog of foxi1, which is also sufficient to promote the formation of PSC precursors. Strikingly, the PSCs form in the skin as two distinct subtypes that resemble the alpha-and beta-intercalated cells of the kidney. The alpha-subtype expresses ae1 and localizes H + v-ATPases to the apical plasma membrane, whereas the beta-subtype expresses pendrin and localizes the H + v-ATPase cytosolically or basolaterally. These two subtypes are specified during early PSC differentiation by a binary switch that can be regulated by Notch signaling and by the expression of ubp1, a transcription factor of the grainyhead family. These results have implications for how PSCs are specified in vertebrates and become functionally heterogeneous.

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Origin and Fate of Pendrin-Positive Intercalated Cells in Developing Mouse Kidney

Cited by 23 publications

References 26 publications

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Deletion of hensin/DMBT1 blocks conversion of β- to α-intercalated cells and induces distal renal tubular acidosis

Remodeling of the Fetal Collecting Duct Epithelium

Specification of ion transport cells in theXenopuslarval skin

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