OUR RESEARCH

The eye is an essential organ for animal viability, and as such its appropriate development and function is fundamental for life. For this reason, biological systems have evolved developing mechanisms that enable tissues/organs to compensate for the effect of mutations in genes, preventing their impact on eye development.

Compensatory mechanisms that enable the systems’ robustness can mask the effect of mutations in many genes, showing no overt morphological phenotype and limiting our ability to understand their function. Therefore, relating a phenotype or pathology to a gene represents a major challenge in developmental genetics, and suggests that many genes involved in embryo development or disease remain to be identified.

For example, due to compensatory mechanisms, only ~30% of all the genes that have been linked to anophthalmia (A, no eyes) and microphthalmia (M, small underdeveloped eyes) show a clear eye phenotype when knocked down in animal models. This limits the use of animal models to validate new A/M candidate genes identified in patients, or studying the cellular and molecular mechanisms behind these congenital malformations.

 Outreach

This is a 15-minute cut of a longer documentary, including our lab’s research (min 11.43), showcasing some of the beauty and translatability of developmental biology research being undertaken currently throughout labs in the UK. Alice Roberts talks us through the wonder of developmental biology, and Courtney Lancaster (and her twin sister) tour various labs and interview PIs working with several model organisms to find out what drives various elements of embryo development, and how their studies may one day impact the clinic.

 Current Lab Members

Collaborators

Gavin Arno (Greenwood Genetic Center, US)
Brian Brooks (NIE, US)
Genomics England (UK)
Lev Parsov (U. Michigan, US)

Previous Lab members

Dr Manuela Lahne-Teaching Lecturer at Queen Mary’s University (2023-24)
Peilin Chen - BSc Biomedical Sciences, UCL (2023-24)
Pablo Paillalí - Research Assistant (2023-24)
María Elisa Cuevas - Biotechnology Engineering, Universidad Católica, Chile (2023-24)
Cristian Aedo  - Biotechnology, Universidad Santo Tomas, Chile (2023-24)
Robin Hayes  - Genetics of human disease, UCL (2022-23)
Karthika Jeganathan –MSc Human Genetics and disease, UCL (2021-22)
Aphena Huang –MSc Human Genetics and disease , UCL (2020-21)
Dr Montserrat Olivares – PostDoc, EMBO short-term fellow (2021)

Selected Publications

Uma M Neelathi, Ehsan Ullah, Aman George, Mara I Maftei, Elangovan Elangovan, Daniel Sanchez-Mendoza, Chloe Adams, David McGaughey, Yuri V Sergeev, Ranya AI Rawi, Amelia Naik, Chelsea Bender, Irene H Maumenee, Michel Michaelides, Tun Giap Tan, Siying Lin, Rafael Villasmil, Delphine Blain, Robert B Hufnagel, Gavin Arno, Rodrigo M Young*, Bin Guan*, Brian P Brooks*
Variants in NR6A1 cause a novel oculo-vertebral-renal (OVR) syndrome.
medRxiv 2024.11.09.24316578; doi: https://doi.org/10.1101/2024.11.09.24316578. *Co-corresponding author.

Powell, G.T., Faro, A., Zhao, Y., Stickney, H., Novellasdemunt, L., Henriques, P., Gestri, G., Redhouse White, E., Ren., J., Lu, W., Young, R.M., Hawkins, T.A., Cavodeassi, F., Schwarz, Q., Dreosti, E., Raible, D.W., Li, V.S.W., Wright, J.W., Jones, Y. and Wilson, S.W. (2024)
Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain.
Science. 384(6695):573-579. doi: 10.1126/science.ade6970.

Young, R.M,* Cavodeassi, F., Hawkins, T.A., Stickney, H.L., Schwarz, Q.P., Lawrence, L.M., Wierzbicki, C., Cheng, B.Y.L., Luo, J., Ambrosio, E.M., Klosner, A., Sealy, I.M., Rowell, J., Trivedi, C.A., Bianco, I.H., Allende, M.L., Busch-Nentwich, E.M., Gestri, G. and Wilson, S.W. (2019) Compensatory mechanisms render Tcf7l1a dispensable for eye formation despite its cell-autonomous requirement in eye field specification.
eLife doi:10.7554/eLife.40093. *Co-corresponding author.

Young, R.M,* Ewan, K.B., Ferrer, V.P., Allende, M.L., Godovac-Zimmermann, J., Dale, T.C., Wilson, S.W. (2019)
Developmentally regulated tcf7l2 alternative splice variants mediate transcriptional repressor functions during eye formation.
eLife doi:10.7554/eLife.51447. *Co-corresponding author.

Holt, R.J.*, Young, R.M.*, Crespo, B., Ceroni, F., Curry, C.J., et al. (2019)
De Novo Missense Variants in FBXW11 Cause Diverse Developmental Phenotypes Including Brain, Eye, and Digit Anomalies.
Am J Hum Genet. 105(3):640-657. doi: 10.1016/j.ajhg.2019.07.005. *Equal contribution

Gaston-Massuet, C., McCabe, M.J., Scagliotti, V., Young, R.M., Carreno, G., et al. (2016)
TCF7L1 is involved in hypothalamo-pituitary axis development.
PNAS. 2;113(5):E548-57. doi: 10.1073/pnas.1503346113.

Moro, E., Ozhan-Kizil G., Mongera, A., Beis, D., Wierzbicki, C., Young, R.M., et al. (2012)
In vivo Wnt signalling tracing through a transgenic biosensor fish reveals novel activity domains.
Dev. Biol. 366:327-40.

Andoniadou, C.L., Signore, M., Young, R.M., Gaston-Massuet, C., Fuchs, E., et al. (2011)
HESX1 and TCF3 mediated repression of Wntß-catenin targets is required for normal development of the anterior forebrain. 
Development. 138:4931-4942.

Valdivia L.E.*, Young R.M.*±, Hawkins T.A., Stickney H.L., Cavodeassi F., et al. (2011)
Lef1-dependent Wnt/ß-catenin signalling drives the proliferative engine that maintains tissue homeostasis during lateral line development.
Development. 138(18):3931-41 * Equal contribution ±Co-corresponding author.

Ewan K, Pajak B, Stubbs M, Todd H, Barbeau O, Quevedo C, Botfield H, Young, R.M., et al. (2010)
A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription.
Cancer Res.15;70(14):5963-73

Our Research is funded by