Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation

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Ihermann-Hella , A , Hirashima , T , Kupari , J , Kurtzeborn , K , Li , H , Kwon , H N , Cebrian , C , Soofi , A , Dapkunas , A , Miinalainen , I , Dressler , G R , Matsuda , M & Kuure , S 2018 , ' Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation ' , Stem cell reports , vol. 11 , no. 4 , pp. 912-928 . https://doi.org/10.1016/j.stemcr.2018.08.012

Title: Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation
Author: Ihermann-Hella, Anneliis; Hirashima, Tsuyoshi; Kupari, Jussi; Kurtzeborn, Kristen; Li, Hao; Kwon, Hyuk Nam; Cebrian, Cristina; Soofi, Abdul; Dapkunas, Arvydas; Miinalainen, Ilkka; Dressler, Gregory R.; Matsuda, Michiyuki; Kuure, Satu
Contributor: University of Helsinki, Helsinki Institute of Life Science HiLIFE
University of Helsinki, Medicum
University of Helsinki, Helsinki Institute of Life Science HiLIFE
University of Helsinki, Helsinki Institute of Life Science HiLIFE
University of Helsinki, Kidney development
University of Helsinki, Medicum
University of Helsinki, Helsinki Institute of Life Science HiLIFE, Infra
Date: 2018-10-09
Language: eng
Number of pages: 17
Belongs to series: Stem cell reports
ISSN: 2213-6711
URI: http://hdl.handle.net/10138/251190
Abstract: The in vivo niche and basic cellular properties of nephron progenitors are poorly described. Here we studied the cellular organization and function of the MAPK/ERK pathway in nephron progenitors. Live-imaging of ERK activity by a Forster resonance energy transfer biosensor revealed a dynamic activation pattern in progenitors, whereas differentiating precursors exhibited sustained activity. Genetic experiments demonstrate that MAPK/ERK activity controls the thickness, coherence, and integrity of the nephron progenitor niche. Molecularly, MAPK/ERK activity regulates niche organization and communication with extracellular matrix through PAX2 and ITGA8, and is needed for CITED1 expression denoting undifferentiated status. MAPK/ERK activation in nephron precursors propels differentiation by priming cells for distal and proximal fates induced by the Wnt and Notch pathways. Thus, our results demonstrate a mechanism through which MAPK/ERK activity controls both progenitor maintenance and differentiation by regulating a distinct set of targets, which maintain the biomechanical milieu of tissue-residing progenitors and prime precursors for nephrogenesis.
Subject: KIDNEY DEVELOPMENT
METANEPHRIC MESENCHYME
SELF-RENEWAL
CELLS
SIX2
GENE
NEPHROGENESIS
ADHESION
KINASES
MORPHOGENESIS
3111 Biomedicine
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