The channel kinase, TRPM7, is required for early embryonic development.
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 brain-specific 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.
Department of Cardiology, Manton Center for Orphan Disease, Children's Hospital Boston, Howard Hughes Medical Institute, Boston, MA 02115, USA.
Jie
J
Jin
Long-Jun
LJ
Wu
Janice
J
Jun
Xiping
X
Cheng
Haoxing
H
Xu
Nancy C
NC
Andrews
David E
DE
Clapham
D000818:Animals; D002454:Cell Differentiation; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D007381:Intermediate Filament Proteins / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000502:physiology; D064231:Nestin; D039904:Pluripotent Stem Cells / Q000166:cytology; D050053:TRPM Cation Channels / Q000502:physiology*
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D050053:TRPM Cation Channels; C421903:Trpm7 protein, mouse