Compensatory growth renders Tcf7l1a dispensable for eye formation despite its requirement in eye field specification

Autor: Young, Rodrigo M, Hawkins, Thomas A, Cavodeassi, Florencia, Stickney, Heather L, Schwarz, Quenten, Lawrence, Lisa M, Wierzbicki, Claudia, Cheng, Bowie Yl, Luo, Jingyuan, Ambrosio, Elizabeth Mayela, Klosner, Allison, Sealy, Ian M, Rowell, Jasmine, Trivedi, Chintan A, Bianco, Isaac H, Allende, Miguel L, Busch-Nentwich, Elisabeth M, Gestri, Gaia, Wilson, Stephen W
Přispěvatelé: Young, Rodrigo M [0000-0001-5765-197X], Hawkins, Thomas A [0000-0003-2921-0004], Cavodeassi, Florencia [0000-0003-4609-6258], Schwarz, Quenten [0000-0002-5958-4181], Wierzbicki, Claudia [0000-0001-7266-2597], Cheng, Bowie Yl [0000-0003-0794-6133], Ambrosio, Elizabeth Mayela [0000-0001-7227-7744], Sealy, Ian M [0000-0002-2890-6635], Rowell, Jasmine [0000-0001-7040-8528], Trivedi, Chintan A [0000-0003-3890-0744], Bianco, Isaac H [0000-0002-3149-4862], Allende, Miguel L [0000-0002-2783-2152], Busch-Nentwich, Elisabeth M [0000-0001-6450-744X], Gestri, Gaia [0000-0001-8854-1546], Wilson, Stephen W [0000-0002-8557-5940], Apollo - University of Cambridge Repository
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: eLife, Vol 8 (2019)
eLife
ISSN: 2050-084X
Popis: The vertebrate eye originates from the eye field, a domain of cells specified by a small number of transcription factors. In this study, we show that Tcf7l1a is one such transcription factor that acts cell-autonomously to specify the eye field in zebrafish. Despite the much-reduced eye field in tcf7l1a mutants, these fish develop normal eyes revealing a striking ability of the eye to recover from a severe early phenotype. This robustness is not mediated through genetic compensation at neural plate stage; instead, the smaller optic vesicle of tcf7l1a mutants shows delayed neurogenesis and continues to grow until it achieves approximately normal size. Although the developing eye is robust to the lack of Tcf7l1a function, it is sensitised to the effects of additional mutations. In support of this, a forward genetic screen identified mutations in hesx1, cct5 and gdf6a, which give synthetically enhanced eye specification or growth phenotypes when in combination with the tcf7l1a mutation.
eLife digest Left and right eyes develop independently, yet they consistently grow to roughly the same size in humans and other creatures. How they do this remains a mystery, though scientists have learned that both eyes originate from a single group of cells in the developing nervous system called the eye field. As development progresses, the eye field splits in two, and buds into the two separate compartments from which each eye forms. As the eyes grow, the cells in each compartment specialize, or ‘differentiate’, to make working left and right eyes. Scientists often study eye development in zebrafish embryos because it is easy to see each step in the process. Now, Young at al. show that zebrafish with a mutation that causes the eye field to be half its normal size go on to form normal-sized eyes. Somehow these developing embryos overcome this deleterious mutation. It turns out that the eyes of zebrafish with this mutation grow for a longer period of time than typical zebrafish eyes. This change allows the mutant fish’s eyes to catch up and reach normal size. When Young et al. removed some cells from one of the forming eyes of normal zebrafish embryos they found that same thing happened. The smaller eye developed for a longer time and delayed its differentiation until both eyes were the same size. Conversely, when eyes developed from a larger than normal eye field, growth stopped prematurely and differentiation began early preventing the eyes from ending up oversized. Though the fish were able to overcome the effects of one mutation to develop normal-sized eyes, adding a second mutation that affected eye development led to unusual sized eyes or absence of eyes. Together the experiments identify genes and mechanisms essential for the formation and size of the eyes. Given that the processes underlying eye formation are very similar in many animals, this new information should help scientists to better understand eye abnormalities in humans.
Databáze: OpenAIRE
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