Biology subjects

Boudreau-Pinsonneault, C.

Publications and source records attributed to Boudreau-Pinsonneault, C..

2 recordsLinked to original sources

bioRxiv2022

Pou3f1 orchestrates a gene regulatory network controlling contralateral retinogeniculate projections

The balance of contralateral and ipsilateral retinogeniculate projections is critical for the establishment of binocular vision, but the transcriptional programs regulating this process remain ill-defined. In this study, we show that the Pou class homeobox protein POU3F1 is selectively expressed in developing mouse contralateral retinal ganglion cells (cRGCs). Inactivation of Pou3f1 increases the number of ipsilateral RGCs produced, leading to abnormal ipsilateral to contralateral projection ratio at the optic chiasm, whereas expression of Pou3f1 in retinal progenitors increases the production of cRGCs. Using Cut&Run and RNA sequencing in wildtype and Pou3f1 mouse knockout retinas, we demonstrate that Pou3f1 is necessary for the establishment of a cRGC gene regulatory network through activation and repression of several known contralateral and ipsilateral determinants, respectively. Finally, we report that POU3F1 is sufficient to induce production of RGC-like cells sending projections to the optic nerve, even in late-stage retinal progenitors not normally competent to generate RGCs. This work uncovers POU3F1 as a master regulator of the cRGC transcriptional program and opens new possibilities for optic nerve regenerative therapies.

developmental biology↗

bioRxiv2021

Direct neuronal reprogramming by temporal identity factors

Temporal identity factors are sufficient to reprogram developmental competence of neural progenitors, but whether they could also reprogram the identity of fully differentiated cells is unknown. To address this question, we designed a conditional gene expression system combined with genetic lineage tracing that allows rapid screening of potential reprogramming factors in the mouse retina. Using this assay, we report that co-expression of the early temporal identity transcription factor Ikzf1, together with Ikzf4, another Ikaros family member, is sufficient to directly convert adult Muller glial cells into neuron-like cells in vivo, without inducing a proliferative progenitor state. scRNA-seq analysis shows that the reprogrammed cells share some transcriptional signatures with both cone photoreceptors and bipolar cells. Furthermore, we show that co-expression of Ikzf1 and Ikzf4 can reprogram mouse embryonic fibroblasts to induced neurons by remodeling chromatin and promoting a neuronal gene expression program. This work uncovers general neuronal reprogramming properties for temporal identity factors in differentiated cells, opening new opportunities for cell therapy development.

neuroscience↗