We are interested in the molecular mechanisms regulating the early eye development and the following processes of cell commitment in the neural retina of the frog Xenopus laevis. We have studied several homeodomain transcription factors that are involved in identifying the initial eye field and in addressing retinal precursor cells (RPCs) toward specific neuronal fates. A complex series of regulatory events ensures that these key regulators are produced in the right time and space within the developing retina to generate the different types of neurons according to a precise and evolutionarily conserved time schedule. In Xenopus, the closely related homeodomain proteins XOTX5b and XOTX2 respectively promote photoreceptor and bipolar cell fates, and, consistent with their expression pattern, have distinct roles in the developing retina. We have identified a small 8-10 aa divergent region, downstream of the homeodomain, that is crucial for the different and specific activities of XOTX2 and XOTX5b: exchange of this “specificity box” between the two proteins, switches the activity of XOTX5b into that of XOTX2 and viceversa. This box also appears relevant for modulating XOTX synergy and interactive abilities of the two XOTXs with NRL, another key regulator of retinal commitment. Photoreceptors and bipolar cells are generated at different time schedules during retinal histogenesis. Interestingly, we found that the two Xotx mRNAs and the mRNA for Xvsx1, another homeobox gene promoting bipolar cell fate, are subject to a tight translational control that allows their respective proteins to be produced according to the different time of generation of photoreceptor and bipolar neurons. This control depends on interactions between their 3’UTRs and specific microRNAs. We have identified candidate microRNAs that are downregulated during retinogenesis to provide the switch for translation of XVSX1 and XOTX2 proteins, therefore allowing their proper timing of expression.
Molecular switches generating cell diversity in the Xenopus retina
VIGNALI, ROBERT
2010-01-01
Abstract
We are interested in the molecular mechanisms regulating the early eye development and the following processes of cell commitment in the neural retina of the frog Xenopus laevis. We have studied several homeodomain transcription factors that are involved in identifying the initial eye field and in addressing retinal precursor cells (RPCs) toward specific neuronal fates. A complex series of regulatory events ensures that these key regulators are produced in the right time and space within the developing retina to generate the different types of neurons according to a precise and evolutionarily conserved time schedule. In Xenopus, the closely related homeodomain proteins XOTX5b and XOTX2 respectively promote photoreceptor and bipolar cell fates, and, consistent with their expression pattern, have distinct roles in the developing retina. We have identified a small 8-10 aa divergent region, downstream of the homeodomain, that is crucial for the different and specific activities of XOTX2 and XOTX5b: exchange of this “specificity box” between the two proteins, switches the activity of XOTX5b into that of XOTX2 and viceversa. This box also appears relevant for modulating XOTX synergy and interactive abilities of the two XOTXs with NRL, another key regulator of retinal commitment. Photoreceptors and bipolar cells are generated at different time schedules during retinal histogenesis. Interestingly, we found that the two Xotx mRNAs and the mRNA for Xvsx1, another homeobox gene promoting bipolar cell fate, are subject to a tight translational control that allows their respective proteins to be produced according to the different time of generation of photoreceptor and bipolar neurons. This control depends on interactions between their 3’UTRs and specific microRNAs. We have identified candidate microRNAs that are downregulated during retinogenesis to provide the switch for translation of XVSX1 and XOTX2 proteins, therefore allowing their proper timing of expression.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
