c-kit delineates a distinct domain of progenitors in the developing kidney.

c-kit delineates a distinct domain of progenitors in the developing kidney. Research Abstract Details 

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c-kit delineates a distinct domain of progenitors in the developing kidney. Abstract Text:

Kai M Schmidt-Ott,Xia Chen,Neal Paragas,Randy S Levinson,Cathy L Mendelsohn,Jonathan Barasch,

Early inductive events in mammalian nephrogenesis depend on an interaction between the ureteric bud and the metanephric mesenchyme. However, mounting evidence points towards an involvement of additional cell types--such as stromal cells and angioblasts--in growth and patterning of the nephron. In this study, through analysis of the stem cell factor (SCF)/c-kit ligand receptor pair, we describe an additional distinct cell population in the early developing kidney. While SCF is restricted to the ureteric bud, c-kit-positive cells are located within the renal interstitium, but are negative for Foxd1, an established marker of stromal cells. In fact, the c-kit-positive domain is continuous with a central mesodermal cell mass ventral and lateral to the dorsal aorta, while Foxd1-expressing stromal cells are continuous with a dorsal perisomitic cell population suggesting distinct intraembryonic origins for these cell types. A subset of c-kit-positive cells expresses Flk-1 and podocalyxin, suggesting that this cell population includes angioblasts and their progenitors. c-kit activation is not required for the survival of these cells in vivo, because white spotting (c-kit(W/W)) mice, carrying a natural inactivating mutation of c-kit, display normal intrarenal distribution of the c-kit-positive cells at E13.5. In addition, early kidney development in these mutants is preserved up to the stage when anemia compromises global embryonic development. In contrast, under defined conditions in organ cultures of metanephric kidneys, c-kit-positive cells, including the Flk-1-positive subset, undergo apoptosis after treatment with STI-571, an inhibitor of c-kit tyrosine phosphorylation. This is associated with reductions in ureteric bud branching and nephron number. Conversely, exogenous SCF expands the c-kit-positive population, including Flk-1-positive angioblasts, and accelerates kidney development in vitro. These data suggest that ureteric bud-derived SCF elicits growth-promoting effects in the metanephric kidney by expanding one or more components of the interstitial c-kit-positive progenitor pool.

c-kit delineates a distinct domain of progenitors in the developing kidney. Publishing Authors By Initials

KM Schmidt-Ott,X Chen,N Paragas,RS Levinson,CL Mendelsohn,J Barasch,

For similar urogenital system: urinary tract: ureter research abstracts see: urogenital system: urinary tract: ureter research

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MEDLINE DATE:

c-kit delineates a distinct domain of progenitors in the developing kidney. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Developmental biology

VOLUME: 299

Page Numbers: 238-49

Journal Abbreviation: Dev. Biol.

ISSN: 0012-1606

DAY: 31

MONTH: 07

YEAR: 2006

c-kit delineates a distinct domain of progenitors in the developing kidney. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 372762

c-kit delineates a distinct domain of progenitors in the developing kidney. Keywords Mesh Terms:

KEYWORDS: Ureter

MESH TERMS: cytology

Chemical & Substance for Abstract: c-kit delineates a distinct domain of progenitors in the developing kidney. Information

Substance Name: Proto-Oncogene Proteins c-kit

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for c-kit delineates a distinct domain of progenitors in the developing kidney.

AFFILIATION: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK-58872

ACRONYM: DK

MEDLINETA: Dev Biol

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