Regulation of long-range BMP gradients and embryonic polarity by propagation of local calcium-firing activity

Hyung Chul Lee; Nidia M M Oliveira; Cato Hastings; Peter Baillie-Benson; Adam A Moverley; Hui-Chun Lu; Yi Zheng; Elise L Wilby; Timothy T Weil; Karen M Page; Jianping Fu; Naomi Moris; Claudio D Stern

doi:10.1038/s41467-024-45772-4

Regulation of long-range BMP gradients and embryonic polarity by propagation of local calcium-firing activity

Nat Commun. 2024 Feb 17;15(1):1463. doi: 10.1038/s41467-024-45772-4.

Authors

Hyung Chul Lee^{1

2}, Nidia M M Oliveira^{3

4}, Cato Hastings³, Peter Baillie-Benson⁵, Adam A Moverley^{3

6}, Hui-Chun Lu^{3

7}, Yi Zheng^{8

9

10}, Elise L Wilby¹¹, Timothy T Weil¹¹, Karen M Page¹², Jianping Fu⁸, Naomi Moris⁵, Claudio D Stern¹³

Affiliations

¹ Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK. [email protected].
² School of Biological Sciences and Technology, College of Natural Sciences, Chonnam National University, 77 Yongbong-ro, Gwangju, 61186, Korea. [email protected].
³ Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK.
⁴ College of Professional Services, Murdoch University, 90 South St, Murdoch, WA, 6150, Australia.
⁵ The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
⁶ Department of Cell and Developmental Biology, Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Centre for Craniofacial & Regenerative Biology, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, Guy's Tower, London, SE1 9RT, UK.
⁸ Departments of Mechanical Engineering, Biomedical Engineering, and Cell & Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
⁹ Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY, USA.
¹⁰ BioInspired Syracuse Institute for Materials and Living Systems, Syracuse University, Syracuse, NY, USA.
¹¹ Department of Zoology, University of Cambridge, Downing Street, Cambridge, CB2 3EJ, UK.
¹² Department of Mathematics, University College London, Gower Street, London, WC1E 6BT, UK.
¹³ Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK. [email protected].

Abstract

Many amniote vertebrate species including humans can form identical twins from a single embryo, but this only occurs rarely. It has been suggested that the primitive-streak-forming embryonic region emits signals that inhibit streak formation elsewhere but the signals involved, how they are transmitted and how they act has not been elucidated. Here we show that short tracks of calcium firing activity propagate through extraembryonic tissue via gap junctions and prevent ectopic primitive streak formation in chick embryos. Cross-regulation of calcium activity and an inhibitor of primitive streak formation (Bone Morphogenetic Protein, BMP) via NF-κB and NFAT establishes a long-range BMP gradient spanning the embryo. This mechanism explains how embryos of widely different sizes can maintain positional information that determines embryo polarity. We provide evidence for similar mechanisms in two different human embryo models and in Drosophila, suggesting an ancient evolutionary origin.

MeSH terms

Animals
Bone Morphogenetic Proteins* / metabolism
Calcium* / metabolism
Chick Embryo
Gastrulation / physiology
Humans
Primitive Streak
Reproduction

Substances

Calcium
Bone Morphogenetic Proteins

Abstract

MeSH terms

Substances

Grants and funding