| First Author | Ihermann-Hella A | Year | 2018 |
| Journal | Stem Cell Reports | Volume | 11 |
| Issue | 4 | Pages | 912-928 |
| PubMed ID | 30220628 | Mgi Jnum | J:333402 |
| Mgi Id | MGI:7438009 | Doi | 10.1016/j.stemcr.2018.08.012 |
| Citation | Ihermann-Hella A, et al. (2018) Dynamic MAPK/ERK Activity Sustains Nephron Progenitors through Niche Regulation and Primes Precursors for Differentiation. Stem Cell Reports 11(4):912-928 |
| abstractText | 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. |
