3D tissue morphogenesis during early zebrafish development
Lead Research Organisation:
University of Warwick
Department Name: Warwick Medical School
Abstract
Our organs have specific shapes and sizes, necessary for efficient function. e.g., lungs are highly branched to optimise gas permeation, whereas skeletal muscle is structured to enable long-ranged force transmission. Errors in formation of organs leads to a host of adult diseases. In the case of the heart, over 40% of human adult heart disease can be traced to a problem that arose during development.
Our understanding of how our organs form is still in its infancy. This is due to two major challenges: (1) human development occurs inside the mother; (2) even for more accessible vertebrates (e.g., fish), imaging of whole organs at sufficient resolution - and performing the subsequent data analysis - has long been a bottleneck.
To circumvent (1), a number of model organisms have been utilised. In particular, the zebrafish has become a powerful system for understanding organ formation - it is a vertebrate, yet it lays transparent embryos in large quantities. For (2), recent advances in optics and machine learning mean we can now collect data of high spatial and temporal resolution to follow single cell behaviour.
We propose to use the developing zebrafish skeletal muscle as a model system to understand how complex form emerges. Muscle fibres consist of slow and fast-twitch fibres. During skeletal muscle formation, these fibres change their morphology, and fast muscle fibres fuse to form multi-nucleated fibres. We have recently built a pipeline to fully segment muscle in 3D during development. Yet, what forces are shaping these cells? We propose to focus on the role of actin in muscle fibre morphogenesis. There appear to be distinct pools of actin, related to cell elongation and fusion. We will dissect these molecular pathways to understand how coordinated actin regulation builds muscle fibres.
This project aligns with MRC focus on Molecular and Cellular Medicine, especially "understanding the mechanisms of development, differentiation, growth and regeneration at the molecular, genetic and cellular levels."
Our understanding of how our organs form is still in its infancy. This is due to two major challenges: (1) human development occurs inside the mother; (2) even for more accessible vertebrates (e.g., fish), imaging of whole organs at sufficient resolution - and performing the subsequent data analysis - has long been a bottleneck.
To circumvent (1), a number of model organisms have been utilised. In particular, the zebrafish has become a powerful system for understanding organ formation - it is a vertebrate, yet it lays transparent embryos in large quantities. For (2), recent advances in optics and machine learning mean we can now collect data of high spatial and temporal resolution to follow single cell behaviour.
We propose to use the developing zebrafish skeletal muscle as a model system to understand how complex form emerges. Muscle fibres consist of slow and fast-twitch fibres. During skeletal muscle formation, these fibres change their morphology, and fast muscle fibres fuse to form multi-nucleated fibres. We have recently built a pipeline to fully segment muscle in 3D during development. Yet, what forces are shaping these cells? We propose to focus on the role of actin in muscle fibre morphogenesis. There appear to be distinct pools of actin, related to cell elongation and fusion. We will dissect these molecular pathways to understand how coordinated actin regulation builds muscle fibres.
This project aligns with MRC focus on Molecular and Cellular Medicine, especially "understanding the mechanisms of development, differentiation, growth and regeneration at the molecular, genetic and cellular levels."
Organisations
People |
ORCID iD |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/W007053/1 | 30/09/2022 | 29/09/2030 | |||
| 2881562 | Studentship | MR/W007053/1 | 01/10/2023 | 29/09/2027 |