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Ragsac, M. F.

Publications and source records attributed to Ragsac, M. F..

2 recordsLinked to original sources

Sensory receptor expansion and neural accommodation in butterfly color vision

The evolution of complex brains required existing neurons and neural circuits to accommodate new inputs. The genetic and developmental mechanisms that enable such integration are largely unknown. Butterflies evolved more complex retinal mosaics through the addition of a second R7 color photoreceptor per ommatidium (unit eye). In Drosophila, the unique R7 makes a stochastic choice to express one of two opsin genes. In butterflies, the two R7s make independent stochastic cell fate choices in each ommatidium, producing three ommatidial types instead of two. Here, we investigate the developmental basis of this change and how the butterfly brain accommodates expanded sensory receptor input. We first identified the changes in gene expression that cause a second R7 cell to be specified. We then modified Drosophila retinas to have butterfly-like transcription factor expression, causing recruitment of an additional R7. The two R7s make independent stochastic choices, like butterflies, leading to three stochastically distributed ommatidial types. In Drosophila, the two R7 subtypes connect to their target neurons, either yDm8 or pDm8. Dm8 neurons of both types are born in excess and Dm8s that do not find connections with their cognate y or pR7s undergo apoptosis. In the presence of extra R7s in butterfly-like fly retinas, additional Dm8s are retained, leading to two Dm8s per medulla column that make appropriate connections with the matching R7 subtypes, facilitating the expansion of color vision. We propose that the presence of cells that would otherwise die provide developmental flexibility that can allow brains to accommodate newly evolved inputs.

developmental biology↗

Diverse logics and grammar encode notochord enhancers

The notochord is a key structure during chordate development. We have previously identified several enhancers regulated by Zic and ETS that encode notochord activity within the marine chordate Ciona robusta (Ciona). To better understand the role of Zic and ETS within notochord enhancers, we tested 90 genomic elements containing Zic and ETS sites for expression in developing Ciona embryos using a whole-embryo, massively parallel reporter assay. We discovered that 39/90 of the elements were active in developing embryos; however only 10% were active within the notochord, indicating that more than just Zic and ETS sites are required for notochord expression. Further analysis revealed notochord enhancers were regulated by three groups of factors: (1) Zic and ETS, (2) Zic, ETS and Brachyury (Bra), and (3) Zic, ETS, Bra and FoxA. One of these notochord enhancers, regulated by Zic and ETS, is located upstream of laminin alpha, a gene critical for notochord development in both Ciona and vertebrates. Reversing the ETS sites in this enhancer greatly diminish expression, indicating that enhancer grammar is critical for enhancer activity. Strikingly, we find clusters of Zic and ETS binding sites within the introns of mouse and human laminin alpha 1 with conserved enhancer grammar. Our analysis also identified two notochord enhancers regulated by Zic, ETS, FoxA and Bra binding sites: the Bra Shadow (BraS) enhancer located in close proximity to Bra, and an enhancer located near the gene Lrig. Randomizing the BraS enhancer demonstrates that although the Zic and ETS sites are necessary for enhancer activity, they are not sufficient. We find that FoxA and Bra sites contribute to BraS enhancer activity. Zic, ETS, FoxA and Bra binding sites occur within the Ciona Bra434 enhancer and vertebrate notochord Brachyury enhancers, suggesting a conserved regulatory logic. Collectively, this study deepens our understanding of how enhancers encode notochord expression, illustrates the importance of enhancer grammar, and hints at the conservation of enhancer logic and grammar across chordates.

developmental biology↗