Associate Professor
Rodrigo studied Biochemistry (University of Chile) and completed his PhD in the laboratory of Miguel Allende (University of Chile, CONICYT scholarship) and Nancy Hopkins (MIT, Fulbright fellowship). He then pursued his postdoc in Steve Wilson's laboratory (UCL, Marie Curie - Incoming International Fellowship), where he began studying eye development in zebrafish.
His laboratory focuses on studying the molecular and genetic bases of eye development and the modelling of congenital eye diseases using zebrafish as an animal model. In particular, aiming to understand the molecular and cellular mechanisms that compensate for the effect of mutations during early eye development.
PUBLICATIONS
Neelathi UM, Ullah E, George A, Maftei MI, Elangovan E, Sanchez-Mendoza D, Adams C, McGaughey D, Sergeev YV, Rawi RAI, Naik A, Bender C, Maumenee IH, Michaelides M, Tan TG, Lin S, Villasmil R, Blain D, Hufnagel RB, Arno G, Young RM*, Guan B*, Brooks BP*. (2024) 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 is a novel Frizzled- and LRP6-interacting protein required for neurons to acquire left-right asymmetric character. Science. DOI:10.1126/science.ade6970.
Owen, N., Toms, M., Young, R.M., Eintracht, J., Sarkar, H., Genomics England Research Consortium, Brooks, B.P. and Moosajee, M. (2023) Loss of the crumbs cell polarity complex disrupts epigenetic transcriptional control and cell cycle progression in the developing retina. The Journal of Pathology. 259 (4):441-454.
Gilbert, R.M., Sumodhee, D., Pontikos, N., Hollyhead, C., Patrick, A., Scarles, S., Van Der Smissen, S., Young, R.M., Nettleton, N., Webster, A.R., Cammack, J. (2022) Collaborative Research and Development of a Novel, Patient-Centered Digital Platform (MyEyeSite) for Rare Inherited Retinal Disease Data: Acceptability and Feasibility Study. JMIR Form Res. 31;6(1):e21341. doi: 10.2196/21341.
Owen, N., Toms, M., Young. R.M., Eintracht, J., Sarkar, H., Brooks, B.P., Moosajee, M. (2022) Genomics England Research Consortium. Identification of 4 novel human ocular coloboma genes ANK3, BMPR1B, PDGFRA, and CDH4 through evolutionary conserved vertebrate gene analysis. Genet Med. 13:S1098-3600 (21) 05473-3. DOI: 10.1016/j.gim.2021.12.014.
Young, R.M.,* Solis, C.J., Barriga-Fehrman, A., Abogabir, C., Thadani, A.R., Labarca, M., Bustamante, E., Tapia, C.V., Sarda, A.G., Sepulveda, F., Pozas, N., Cerpa, L.C., Lavanderos, M.A., Varela, N.M., Santibañez, A., Sandino, A.M., Reyes-Lopez, F., Dixon, G. and Quiñones, L.A. (2021) Smartphone Screen Testing, a novel pre-diagnostic method to identify SARS-CoV-2 infectious individuals. eLife 10.7554/eLife.70333 *Co-corresponding author.
Hay, E., Henderson, R., Mansour, S., Deshpande, C., Jones, R.l., Nutan, S., Mankat, K., Young, R.M., Moosajee, M., Arno, G. (2020) Expanding the phenotypic spectrum consequent upon de novo WDR37 missense variants. Clin. Genet. 98(2):191-97.
Varga, M., Csalyi, K., Bertyak, I., Menyhard, D. K., Poole, R.J., Cerveny, K.L., Kovesdi, D., Baratki, B., Rouse, H., Vad, K., Hawkins, T.L., Stickney, H.L., Cavodeassi, F., Schwarz, Q., Young, R.M. and Stephen W. Wilson (2020) The GINS complex is required for the survival of rapidly proliferating retinal and tectal progenitor cells during zebrafish development. Front. Cell Dev. Biol.
Young, R.M,* Ewan, K.B., Ferrer, V.P., Allende, M.L., Godovac-Zimmermann, J., et al. (2019) Developmentally regulated tcf7l2 alternative splice variants mediate transcriptional repressor functions during eye formation. eLife 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 *Equal contribution
Young, R.M,* Cavodeassi, F., Hawkins, T.A., Stickney, H.L., Schwarz, Q.P., et al. (2019) Compensatory mechanisms render Tcf7l1a dispensable for eye formation despite its cell-autonomous requirement in eye field specification. eLife 10.7554/eLife.40093. *Co-corresponding author.
Richardson, R., Owen, N., Toms, M., Young, R.M., Tracey-White, D. and Moosaje, M. (2019) Transcriptome profiling of zebrafish optic fissure fusion. Scientific Reports, 9(1),:1540.
Valdivia L.E., Lamb, D.B., Horner, W., Wierzbicki, C., Tafessu, A., et al. (2016) Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish. Development, 143(7):1087-98.
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, 113 (5):548-57.
Hüsken, U., Stickney, H.L., Gestri, G., Bianco, I.H., Faro, A., Young, R.M., et al. (2014) Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons. Current Biology. 24(19):2217-27.
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
*Co-First Author ±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
(Book Ch.) Cavodeassi, F., Kapsimali, M., Wilson, S.W. and Young, R.M. (2009) Forebrain: Early Development. In: Squire LR (ed.) Encyclopedia of Neuroscience, volume 4, pp. 321-325. Oxford: Academic Press.
Cavodeassi, F., Carreira-Barbosa, F., Young, R.M., Concha, M.L., Allende, M.L., et al. (2005) Early Stages of Zebrafish Eye Formation Require the Coordinated Activity of Wnt11, Fz5, and the Wnt/ -Catenin Pathway. Neuron 47:1-14.
Young, R.M., Reyes, A. and Allende, M.L. (2002) Expression and splice variant analysis of the zebrafish tcf-4 transcription factor. Mech. Dev. 117:269-273.
Young, R.M., Marty, S., Nakano, Y., Wang, H., Yamamoto, D., et al. (2002) Zebrafish yolk-specific not really started (nrs) gene is a vertebrate homolog of the Drosophila spinster gene and is essential for embryogenesis. Dev. Dyn. 223:298-305.
Mayor, R., Guerrero, N. Young, R.M., Gomez-Skarmeta, J.L. and Cuellar, C. (2000) A novel function for the Xslug gene: control of the dorsal endomesoderm by repressing BMP-4. Mech. Dev. 97, 47-56
Mayor, R., Young, R.M. and Vargas, A. (1999) Development of the neural crest in Xenopus. Curr. Top. Dev. Biol. 43:85-113.
RESEARCH LINES
The eye is an essential organ for the viability of animals, and as such, its proper development is essential for life. For this reason, evolution has developed mechanisms that compensate for the effect of mutations in genes or morphological alterations, preventing their impact on eye development. One of them, growth compensation (Young et al., 2019), allows the eyes to reach their expected size even when they start developing from a primordium with half the number of cells, and can mask the effect of mutations that lead to a smaller eye primordium.
Our lab studies the cellular and molecular mechanisms that modulate the balance of proliferation and differentiation of retinal progenitors that enable the phenomenon of growth compensation. We also study new cellular and molecular functions of genes involved in eye formation, in which mutations give rise to congenital eye globe defects in humans.
Mutations in genes can affect embryonic development and lead to the birth of children with smaller eyes (microphthalmos, M), or without eyes (anophthalmos, A). These conditions can be unilateral or bilateral in more severe cases, and mutations in approximately 100 genes have been linked to A/M patients. The genetic diagnosis of these patients allows timely genetic counselling to improve their quality of life.
In Chile, there is no national plan for the molecular diagnosis of these cases, therefore our lab has started to recruit A/M patients to evaluate mutations that may be present in genes already associated with A/M, or find new genes associated with these pathologies. The function of the new genes that we find will be studied by generating similar mutations in zebrafish to evaluate their effect on eye development.
PROJECTS
Active
2022-2025 FONDECYT Regular 1221843 (Investigador Principal)
Completed
2021-2022 CORFO Crea y Valida I+D 21CVID-171973 (Investigador Principal)
TEAM
Current
Katherine Cid, Biologist, University of Concepción, Laboratory Manager/Research Assistant.
Gonzalo Mellado, Professional Practice, Marine Biology, Universidad Andrés Bello
Ana Carolina Castillo – Professional Practice, Chemistry and Pharmacy, Universidad de Chile.
Former Lab Members
Till Stoltenow Undergraduate research stage, Molecular Medicine, University of Tübingen.
Pablo Paillalí, Laboratory Manager/Research Assistant.
Elisa Cuevas, Undergraduate thesis, Biotechnology Engineering, Catholic University of Chile. Now working at Oncobiomed.
Cristian Aedo, Undergraduate thesis, Biotechnology, University Santo Tomás.
NETWORK
National
Kenneth Jonson – Universidad de Chile
Joaquin Letelier – Universidad Mayor
International
Gavin Arno – Institute of Ophthalmology, UCL, UK.
Brian Books – National Eye Institute, USA.
Florencia Cavodeassi – St Georges University, London, UK.
David Miguez – Universidad Autónoma de Madrid, Spain.