Overview of the lab
We are interested in the regulatory mechanisms underlying retina ontogenesis. For the past years, we have explored how the proneural proteins ATOH7 and NEUROGENIN 2 regulate the conversion of proliferating progenitor cells into differentiated neurons in the developing retina.
ATOH7-mediated transcriptional network underlying neurogenesis in retina
Retinal ganglion cells (RGCs) are the output neurons of the retina and are the first to die in human retinopathies leading to blindness. In view of replacements therapies, the question as to how progenitor cells commit towards the RGC fate in vivo is in the focus of attention in the developmental and regenerative neurobiology fields. We have developed experimental approaches to map the transcriptional network underlying retina ontogenesis and to schedule, in real time, the transition from neural progenitor cells into differentiated RGCs. Identification of cis-acting regulatory elements in genes expressed in retinal progenitor cells and in RGCs, gene expression analysis under normal and transcription factor perturbation conditions and the production of “ChIP-grade” antibodies against the chicken ATOH7, NGN2 and NEUROM (NEUROD4) proteins enabled us to achieve one of the first demonstrations of correlation between gene expression, binding of transcription factors and chromatin modification in a developing chick and mouse neural tissues. Chromatin immunoprecipitation coupled to DNA microarray (ChIP-on-chip) experiments led us to identify important targets for gene regulatory network mapping in the embryonic chick retina. Currently, a major effort is concentrated on the ATOH7-mediated regulation of cell-cycle progression, fate choices and cell metabolism during retina development.
Biogenesis and dynamic subcellular distribution of mitochondria
The transition from multipotent dividing progenitors to differentiated neurons involves changes in the way cells produce energy. Glycolysis has been associated with actively dividing progenitors, while differentiated cells rely mainly on oxidative phosphorylation for energy supply. We analyze how the switch from the glycolysis to oxidative phosphorylation is related to the onset of differentiation and, in particular, how this process is related to mitochondria biogenesis. Currently, we explore how ATOH7 orchestrates the interplay between biogenesis of mitochondria, cell cycle progression and RGC differentiation in the retina.
Interspecies differences in the assembly of the embryonic retina
Although the plan of the retina is well conserved across vertebrate species, there are considerable variations in cell-type diversity and cell-type number as well as in the organization and properties of the tissue that reflect differences in eye ontogenesis. Because high visual acuity requires a high ratio of RGC to photoreceptors, the proportion of progenitor cells recruited to produce RGCs in the developing retina contributes to the functional characteristics of the adult eye. In diurnal birds, the ratio of RGC to photoreceptors is high (e.g., chicken) or very high (e.g., pigeon) and birds have a high visual acuity but a low sensitivity. In mammals this ratio is much lower and despite causing lower visual acuity, it increases sensitivity and had a beneficial influence on adaptation of mammals to night vision. We explore how interspecies differences in the Atoh7-mediated transcriptional networks underlay variations in the production of RGCs in the chick, the pigeon and the mouse retinas.