Challenging key concepts in neural differentiation: the role of neuromesodermal progenitors in patterning the head-to-tail axis in vertebrates
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Biological Sciences
Abstract
In this project, this question will be investigated both in vitro in mouse pluripotent cells, and in two in vivo systems, mouse and chick embryos.
NMPs are characterised by the coexpression of two transcription factors, T(brachyury) and Sox2. Meanwhile Sox1 expression characterises the site of future brain formation. Since we have fluorescent markers of these populations, this is a tractable in vitro system to follow the sequence of cell fate decisions needed to make brain and spinal cord at the single cell level. Analysis of single cell transcriptomes in parallel with analysis of their commitment will further characterise these cell fate decisions. Furthermore, in vitro culture of manipulated early mouse and embryos where future brain and spinal cord tissue are challenged by transplantation to spinal cord or brain environments respectively will test at what stage these cells are committed to brain or spinal cord fates: before or after their commitment to a neural identity. Our preliminary data suggests a rather similar sequence of events in each organism, but subtle differences in the generation of these anterior and posterior cell types may underpin some of the species differences; this will be analysed by comparison of chick and mouse transcriptomes.
This project therefore challenges a fundamental concept in developmental biology, but also is likely to lead to improvements in the in vitro differentiation of pluripotent cells into cell types of clinical interest for degenerative disease and/or injury.
NMPs are characterised by the coexpression of two transcription factors, T(brachyury) and Sox2. Meanwhile Sox1 expression characterises the site of future brain formation. Since we have fluorescent markers of these populations, this is a tractable in vitro system to follow the sequence of cell fate decisions needed to make brain and spinal cord at the single cell level. Analysis of single cell transcriptomes in parallel with analysis of their commitment will further characterise these cell fate decisions. Furthermore, in vitro culture of manipulated early mouse and embryos where future brain and spinal cord tissue are challenged by transplantation to spinal cord or brain environments respectively will test at what stage these cells are committed to brain or spinal cord fates: before or after their commitment to a neural identity. Our preliminary data suggests a rather similar sequence of events in each organism, but subtle differences in the generation of these anterior and posterior cell types may underpin some of the species differences; this will be analysed by comparison of chick and mouse transcriptomes.
This project therefore challenges a fundamental concept in developmental biology, but also is likely to lead to improvements in the in vitro differentiation of pluripotent cells into cell types of clinical interest for degenerative disease and/or injury.