Eya1 interacts with Six2 and Myc to regulate expansion of the nephron progenitor pool during nephrogenesis

Jinshu Xu, Elaine Y.M. Wong, Chunming Cheng, Jun Li, Mohammad T.K. Sharkar, Chelsea Y. Xu, Binglai Chen, Jianbo Sun, Dongzhu Jing, Pin Xian Xu

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Self-renewal and proliferation of nephron progenitor cells and the decision to initiate nephrogenesis arecrucial events directing kidney development. Despite recent advancements in defining lineage and regulators for the progenitors, fundamental questions about mechanisms driving expansion of the progenitors remain unanswered. Here we show that Eya1 interacts with Six2 and Myc to control self-renewing cell activity. Cell fate tracing reveals a developmental restriction of the Eya1+ population within the intermediate mesoderm to nephron-forming cell fates and a common origin shared between caudal mesonephric and metanephric nephrons. Conditional inactivation of Eya1 leads to loss ofSix2 expression and premature epithelialization ofthe progenitors. Six2 mediates translocation of Eya1 to the nucleus, where Eya1 uses its threonine phosphatase activity to control Myc phosphorylation/dephosphorylation and function in the progenitor cells. Our results reveal a functional link between Eya1, Six2, and Myc in driving the expansion and maintenance of the multipotent progenitors during nephrogenesis.

Original languageEnglish
Pages (from-to)434-447
Number of pages14
JournalDevelopmental Cell
Volume31
Issue number4
DOIs
StatePublished - 24 Nov 2014

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