The channel kinase, TRPM7, is required for early embryonic development

Jie Jin, Long-Jun Wu, Janice Jun, Xiping Cheng, Haoxing Xu, Nancy C. Andrews, David E. Clapham

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Global disruption of transient receptor potential-melastatin-like 7 (Trpm7) in mice results in embryonic lethality before embryonic day 7. Using tamoxifen-inducible disruption of Trpm7 and multiple Cre recombinase lines, we show that Trpm7 deletion before and during organogenesis results in severe tissue-specific developmental defects. We find that Trpm7 is essential for kidney development from metanephric mesenchyme but not ureteric bud. Disruption of neural crest Trpm7 at early stages results in loss of pigment cells and dorsal root ganglion neurons. In contrast, late disruption of brainspecific Trpm7 after embryonic day 10.5 does not alter normal brain development. We developed induced pluripotent stem cells and neural stem (NS) cells in which Trpm7 disruption could be induced. Trpm7 -/- NS cells retained the capacities of self-renewal and differentiation into neurons and astrocytes. During in vitro differentiation of induced pluripotent stem cells to NS cells, Trpm7 disruption prevents the formation of the NS cell monolayer. The in vivo and in vitro results demonstrate a temporal requirement for the Trpm7 channel kinase during embryogenesis.

Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number5
DOIs
StatePublished - Jan 31 2012

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Neural Stem Cells
Embryonic Development
Phosphotransferases
Induced Pluripotent Stem Cells
Neurons
Organogenesis
Neural Crest
Spinal Ganglia
Mesoderm
Tamoxifen
Astrocytes
Kidney
Brain
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Chanzyme
  • Gastrulation
  • Magnesium
  • Melanocytes
  • TRPM6

Cite this

Jin, Jie ; Wu, Long-Jun ; Jun, Janice ; Cheng, Xiping ; Xu, Haoxing ; Andrews, Nancy C. ; Clapham, David E. / The channel kinase, TRPM7, is required for early embryonic development. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 5.
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The channel kinase, TRPM7, is required for early embryonic development. / Jin, Jie; Wu, Long-Jun; Jun, Janice; Cheng, Xiping; Xu, Haoxing; Andrews, Nancy C.; Clapham, David E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 5, 31.01.2012.

Research output: Contribution to journalArticle

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