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Biol Open. 2017 Oct 15;6(10):1458-1471. doi: 10.1242/bio.026039.

SERCA directs cell migration and branching across species and germ layers.

Author information

1
Division of Biological Sciences, California Institute of Technology, Pasadena, CA 91125, USA dvbrown@post.harvard.edu.
2
The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
3
Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland, and the Department of Biomedical Research, University of Bern, 3008 Bern, Switzerland.
4
Department of Biochemistry & Centre for Cell Imaging, Institute of Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK.
5
Division of Child Health, Institute of Translational Medicine, University of Liverpool, Liverpool L12 2AP, UK.
6
Craniofacial Biology, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA 90089, USA.
7
Division of Biological Sciences, California Institute of Technology, Pasadena, CA 91125, USA.
8
Biological Sciences and Molecular and Computational Biology, Translational Imaging Center, University of Southern California, Los Angeles, CA 90089, USA.
9
Center for Space and Habitability, University of Bern, 3012 Bern, Switzerland.
10
Biological Sciences and Biomedical Engineering, University of Southern California, Los Angeles, CA 90089, USA.
11
NHS Lothian, Edinburgh, EH14 1TY, UK.

Abstract

Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca2+ reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca2+ levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca2+ differential, aborting both cell migration and new branching. Activating protein kinase C (PKC) rescued Ca2+ in tip cells and restored cell migration and branching. Likewise, inhibiting SERCA abolished mammalian epithelial budding, PKC activation rescued budding, while morphogens did not. Mesoderm (zebrafish angiogenesis) and ectoderm (Drosophila nervous system) behaved similarly, suggesting a conserved requirement for cell-autonomous Ca2+ signaling, established by SERCA, in iterative budding.

KEYWORDS:

Branching morphogenesis; Calcium dynamics; Cell migration; SERCA

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