Active Genetics & Molecular Biology Cells, Biochemistry & Physiology

Epithelial to mesenchymal plasticity in the ventral forebrain

Funder Wellcome Charity-funded
Recipient organisation University of Sheffield
Funding £1.6M
Period Aug 2024 — Jul 2028

In plain English

AI plain-English summary

Cells in the chick embryo’s developing forebrain can change shape and migrate to form the hypothalamus, the gut, and a hormone-producing gland called Rathke’s pouch—challenging the textbook view that these tissues arise from separate lineages. This matters because the tuberal hypothalamus controls appetite, metabolism, stress, and reproduction. How its cells are specified during embryogenesis is poorly understood. The standard model—that a simple gradient of signalling molecules stamps out different fates—cannot explain how the same group of cells ends up in the brain, the gut, and the pituitary. The researchers suspect that a process called epithelial-to-mesenchymal plasticity, driven by TGFβ signals, lets these cells detach, move, and adopt different identities. If the team confirms this, it would rewrite the developmental map of the forebrain and gut. Understanding how cells switch between anchored and migratory states could also illuminate what goes wrong in congenital disorders affecting the hypothalamus, pituitary, or foregut, and may eventually inform tissue engineering or regenerative medicine. For now, the work is fundamental science—asking how embryos build complex organs from a simple sheet of cells, a question whose answers have historically reshaped medicine in unpredictable ways.

View original technical description
How, when and where are cells specified to different fates during embryogenesis to form functional organs? Specification of the neural tuberal hypothalamus has long been thought to occur through a patterning mechanism, mediated by graded morphogen signals. Furthermore, tuberal hypothalamic cells are classically thought to be distinct in lineage from endoderm. Our work challenges these ideas. Previously we showed that tuberal specification is linked to growth, tuberal cells generated as a wave of BMP signalling sweeps through hypothalamic floor plate-like (HypFP) cells. Pilot studies, including scRNA-seq studies, multiplex HCR, fate-mapping and analyses of cell behaviours in static images, indicate that HypFP cells may contribute cells to the tuberal progenitor region, Rathke’s pouch and the foregut. Here we will take a multi-pronged in vivo and ex vivo approach in the chick embryo, including clonal lineage analysis, live-imaging, and functional studies to ask: Do HypFP cells demonstrate epithelial-to-mesenchymal plasticity, enabling them/their descendants to migrate? How do candidate molecules - in particular those in a TGFβ signalling network - direct HypFP/downstream progenitor programmes, influence their epithelial characteristics and support alternate fates? When and where are distinct fates specified in HypFP-derived cells?

View the original record at the funder ↗

Researchers

Marysia Placzek (EPMC Awardee)

Related Research

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Original classification

Discovery Award

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.