Santos Lab | Evolutionary Logic of Amniogenesis - lessons from stem cell models

A 2027 Crick PhD project with Silvia Santos.

The amnion is one of evolution's most transformative innovations—a protective membrane that enabled vertebrates to reproduce on land and paved the way for the extraordinary diversity of reptiles, birds and mammals. Yet despite its pivotal role in evolution and its essential functions during embryonic development and pregnancy, how the amnion forms remains surprisingly poorly understood.

Across most studied species the amnion forms after germ layer specification during gastrulation. In mouse and chicken for example, it emerges through a coordinated folding process that physically elevates and encloses the embryo. Strikingly, humans represent a major developmental exception: the amnion forms during implantation prior to gastrulation and arises through cavitation rather than folding. Thus although the amnion performs a conserved function across species, its timing, morphogenetic mechanism and potentially regulatory logic differ.

We lack a mechanistic and evolutionary explanation for how humans deviate from the canonical post-gastrulation program.

To address this gap, we will take a comparative evolutionary approach to define how developmental diversity arose in a tissue with conserved function but divergent formation strategies. inspired by our recent work[1] we will be using embryonic stem cells of three different species and establish culture conditions to generate 3D stem cell-based models of the amnion in different species.

This project will: a) define and compare the signaling requirements for amnion specification across species; b) quantitatively characterize amnion morphogenesis using long term light-sheet imaging and c) determine what transcription factors drive amniogenesis.

Together, this comparative strategy will establish whether the human amnion represents a temporal shift of an ancestral program or a fundamentally distinct developmental solution, providing an evolutionary framework for understanding amniogenesis across vertebrates.

The successful candidate will be exposed to a collaborative, inter-disciplinary and supportive environment and be trained and develop skills in quantitative imaging, advanced sequencing, stem cell biology, 3D (organoid) models of early development, screening and automation, CRISPR and biosensors.

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This project will suit any candidate who is intrigued by Cell and Developmental Biology, Stem Cell Biology and 3D models of early development. Any degree in the Life Sciences or a background in relevant areas to Cell, Developmental and Quantitative Biology is suitable for applying for this studentship. A strong motivation to be exposed to different state of the art techniques including single cell technologies, 3D organoid models, OMICS and imaging is expected.

Motivation to be part and contribute to an interdisciplinary, highly collegial and collaborative environment is an essential.

1) Think about a lecture, a seminar or a paper you recently read and that had an impact on you. Tell us what it was about and why it was memorable to you.

OR

2) Looking at the research undertaken in our lab, what aspect would you be most interested in exploring further? What perspective, skill or approach would you bring to investigating it.

Post-gastrulation amnioids as a stem cell-derived model of human extra-embryonic development.

1. Dobreva, M.P., Pereira, P.N., Deprest, J. and Zwijsen,

A. (2010)

On the origin of amniotic stem cells: of mice and men.

2. Thowfeequ, S., Hanna, C.W. and Srinivas, S. (2025)

Origin, fate and function of extraembryonic tissues during mammalian development.

3. Gunne-Braden,

A., Sullivan,

A., Gharibi,

B., Sheriff, R.S.M., Maity,

A., Wang, Y.F., . . Santos, S.D.M. (2020)

GATA3 Mediates a Fast, Irreversible Commitment to BMP4-Driven Differentiation in Human Embryonic Stem Cells.

Combinatorial BMP4 and activin direct the choice between alternate routes to endoderm in a stem cell model of human gastrulation.