SERCA directs cell migration and branching across species and germ layers
Creators
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1.
California Institute of Technology
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2.
Children's Hospital of Los Angeles
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3.
University Hospital of Bern
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4.
University of Bern
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5.
University of Liverpool
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6.
University of Southern California
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7.
NHS Lothian
Abstract
Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca^(2+) 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 Ca^(2+) levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca^(2+) differential, aborting both cell migration and new branching. Activating protein kinase C (PKC) rescued Ca^(2+) 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 Ca^(2+) signaling, established by SERCA, in iterative budding.
Additional Information
© 2017 Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received April 26, 2017; Accepted August 14, 2017; Published online October 15, 2017. We thank Sean McCann for his assistance with the migration and shedding assays, and Kai Zinn and Hyung-Kook Lee for advice on the Drosophila embryo studies. The authors declare no competing or financial interests. Author contributions: Conceptualization: E.C.J., D.V.B.; Methodology: D.V.B., N.L., S.N., T.V.T., N.C.F., M.G.C., D.A., M.R.F., L.A.T., G.E.F., D.W., S.E.F., D.B., E.C.J.; Software: D.V.B., D.J.B.; Validation: D.V.B., N.L., D.B., E.C.J.; Formal analysis: D.V.B., N.L., S.N., N.C.F., M.G.C., D.A., M.R.F., G.E.F., D.B., E.C.J.; Investigation: D.V.B., N.L., S.N., T.V.T., N.C.F., M.G.C., D.A., M.R.F., G.E.F., E.C.J.; Resources: D.V.B., N.L., T.V.T., N.C.F., M.G.C., M.R.F., L.A.T., D.W., S.E.F., D.B., E.C.J.; Data curation: D.V.B., N.L., S.N., N.C.F., M.G.C., D.A., M.R.F., G.E.F., E.C.J.; Writing - original draft: D.V.B., E.C.J.; Writing - review & editing: D.V.B., N.L., S.N., M.R.F., L.A.T., G.E.F., D.W., S.E.F., D.B., E.C.J.; Visualization: D.V.B., D.J.B., E.C.J.; Supervision: D.W., S.E.F., D.B., E.C.J.; Project administration: D.V.B., E.C.J.; Funding acquisition: D.V.B., D.W., S.E.F., D.B., E.C.J. Funding: D.V.B. was funded by the National Institutes of Health (NHLBI) grant no. NRSA 1F30 HL110723, National Institutes of Health FaceBase grant no. U01 DE020063 and the Pasadena Guild Endowment of Children's Hospital Los Angeles. N.L. was funded by the Royal College of Surgeons of England and The Wellcome Trust, UK grant no. WT090124MA. S.N. was funded by a HURM graduate student supplement to the National Institutes of Health grant no. NIGMS R01GM096195 (D.W. as co-PI) and DE training grant T90 DE021982. N.C.F. was funded by The Royal College of Surgeons of England and the Medical Research Council, UK. M.R.F. is funded by National Institutes of Health award R03DK090295, and a Senior Research Award from the Crohn's and Colitis Foundation of America. D.W. was funded by the National Institutes of Health HL44060, 44977, 60231 and 12268, California Institute for Regenerative Medicine Training Grant TG2-01168 and Shared Laboratory Grant CL1-00507, the Garland Foundation, the Webb Foundation, the Pasadena Guild Endowment of Children's Hospital Los Angeles and the St Andrew's Society of Los Angeles. D.B. was funded by the Medical Research Council, UK grant no. MR/K015931/1. E.C.J. was funded by a Medical Research Council New Investigator Award grant no. G0802057, a Medical Research Council Centenary Award and an American Asthma Foundation Early Excellence Award grant no. 11-0051.Attached Files
Published - 1458.full.pdf
Supplemental Material - BIO026039supp.pdf
Supplemental Material - BIO026039supp1.pdf
Files
1458.full.pdf
Additional details
Identifiers
- PMCID
- PMC5665464
- Eprint ID
- 82928
- Resolver ID
- CaltechAUTHORS:20171103-082000956
Funding
- NIH Postdoctoral Fellowship
- 1F30 HL110723
- NIH
- U01 DE020063
- Children's Hospital Los Angeles Pasadena Guild
- Royal College of Surgeons of England
- Wellcome Trust
- WT090124MA
- NIH
- R01GM096195
- NIH Predoctoral Fellowship
- T90 DE021982
- Medical Research Council (UK)
- MR/K015931/1
- NIH
- R03DK090295
- Crohn's and Colitis Foundation of America
- NIH
- HL44060
- NIH
- HL44977
- NIH
- HL60231
- NIH
- HL12268
- California Institute for Regenerative Medicine
- TG2-01168
- Children's Hospital Los Angeles
- CL1-00507
- John Jewett and Helen Chandler Garland Foundation
- Del Webb Foundation
- St Andrew's Society of Los Angeles
- Medical Research Council (UK)
- G0802057
- American Asthma Foundation
- 11-0051
Dates
- Created
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2017-11-03Created from EPrint's datestamp field
- Updated
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2022-03-23Created from EPrint's last_modified field