Andrew Nelson

As embryos develop they become more complex, acquiring progressively more cell types in order to form fully functional tissues and organs. Emergence of new cell types during development is highly coordinated in time and space. This coordination involves the activation and deactivation of specific sets of genes through multiple waves of programming, largely controlled by signals received from neighbouring cells and local tissue environments. Whether genes are activated or deactivated is heavily influenced by regulatory DNA sequences, and whether they are accessible to the relevant cellular machinery. We seek to understand how cues received by cells influences use of different DNA sequences by specialised proteins to activate and deactivate genes, and thus control cell identities. The Nelson lab studies how cell identities are determined in two distinct contexts. We use zebrafish and human embryonic stem cells to investigate how specialised cells known as “endoderm” arise in the early embryo, and go on to make major contributions to the respiratory and gastrointestinal tracts, and associated organs including liver and pancreas. We also use trophoblast stem cell cultures to investigate how the human and mouse placentas form, and produce specialised cells that enhance blood supply to the developing foetus during pregnancy, and perform nutrient and waste exchange between mother and foetus. Elucidating how programming of different cell types is controlled in zebrafish and mouse has a range of benefits. These include: (1) understanding how such processes likely occur in humans; (2) informing how cells of therapeutic value can be produced in the lab; (3) revealing how errors in gene activation through mutations in DNA can lead to developmental and metabolic defects; and (4) understanding how changes in these fundamental biological processes have driven differences between species during evolution. Our main long-term goal is to understand how mutations in regulatory DNA sequences contribute to developmental defects and pregnancy complications.

Riley, Daniela M., Elsayed, Randa, Walsh, Mark D., Johal, Simaran, Lin, Ying, Walton, Harry, Bretschneider, Till, Ott, Sascha and Nelson, Andrew C. (2026) Functional genomics analysis of developing zebrafish and human endoderm reveals highly conserved cis -regulatory modules acting during vertebrate organogenesis. Genome Research, 36 (4). pp. 695-712. doi:10.1101/gr.280838.125 ISSN 1088-9051. Johal, Simaran, Elsayed, Randa, Wang, Dongfeng, Talbot, Conor D., Feuda, Roberto, Panfilio, Kristen A. and Nelson, Andrew C. (2025) Molecular and functional divergence of zebrafish sox paralogs controlling endoderm formation and left–right patterning. Genome Biology and Evolution, 17 (11). evaf213. doi:10.1093/gbe/evaf213 ISSN 1759-6653.