stem cells in their environment
Professor Marianne Bronner's seminar at King's: "Transcriptional and epigenetic control of neural crest development"
16 September 2013
By Christine Weber
When an embryo begins to develop the structure that will later become its spinal cord, it initially forms the so-called neural tube (see illustration below). This spinal cord precursor structure contains a very special region called the neural crest. The cells building up this region, neural crest cells, do not remain as a stationary component of the central nervous system, but are pinched off when the neural tube closes and start travelling to remote regions in the whole embryo, where they form diverse cellular structures.
The enormous plasticity of neural crest cells is certainly a very interesting phenomenon: these cells give rise to most of the neurons and support cells of the peripheral nervous system, but also to pigment cells, cartilage cells, skeletal muscle and bone cells. This remarkable diversity and multipotency – a very central question to the whole field of developmental biology – has always fascinated Professor Bronner.
Over the years her lab has worked on many different aspects of the neural crest, focussing on the formation of neural crest cells, their migration into various parts of the embryo and how this affects development and cell lineage decisions. Depending on their origin, neural crest cells can differentiate into various different tissues.
Although little is known about how exactly the migration of the neural crest cells – and therefore their eventual fate - is regulated, patterns of gene expression are thought to be involved. Professor Bronner's lab is in the process of delineating a putative vertebrate gene regulatory network where different transcription factors interact with each other to form a molecular cascade of events that guides cell development. Starting with signals from the epidermis and mesoderm (eg Wnt, fibroblast growth factor), distinct sets of transcription factors activate other combinations that in turn establish the neural plate border and activate neural crest specifiers, which finally turn on effector genes to regulate migration and multipotency.
Video about neural crest cell migration -
Hochgreb-Hägele, T., and Bronner, M.E. (2013)
A recent lab focus has been transcriptome analysis to find out more about how neural crest specifiers regulate each other. Indeed, there seem to be significant interactions between sets of genes which control neural specification in a very complex interplay. Just recently the Bronner lab found evidence that a combination of 5 genes is critical for activation of the transcription factor Ets-1 which in turn directly regulates neural crest specifier genes Sox10 and FoxD3.
It might still take a while, but Professor Bronner is determined to identify all the players which are active in the gene regulatory cascade and find out more about where and how they fit into the puzzle. Her lab is also studying various different organisms, from standard models like Xenopus, chick and zebrafish to lampreys and amphioxus to investigate why neural crest cells only exist in vertebrates.
Professor Bronner was certainly able to convey her enthusiasm for her work during the presentation and raised a lot of interesting questions that caused more than one lively discussion afterwards.
• Simoes-Costa, M., Tan-Cabugao, J, Antoshechkin I, Sauka-Spengler, T., Bronner, M.E. (2013) 'Transcriptome analysis reveals novel players in the cranial neural crest gene regulatory network.' Genome Res.
• Hochgreb-Hägele, T., and Bronner, M.E. (2013) 'A novel FoxD3 gene trap line reveals neural crest precursor movement and a role for FoxD3 in their specification.' Dev. Biol. 375, 1-11.
• Green SA, Bronner ME. (2012) 'Gene duplication and the early evolution of neural crest development.' Semin Cell Dev Biol. S1084-9521(12)00230-3 article