Onecut Regulates Core Components of the Molecular Machinery for Neurotransmission in Photoreceptor Differentiation

Abstract

Photoreceptor cells (PRC) are neurons highly specialized for sensing light stimuli and have considerably diversified during evolution. The genetic mechanisms that underlie photoreceptor differentiation and accompanied the progressive increase in complexity and diversification of this sensory cell type are a matter of great interest in the field. A role of the homeodomain transcription factor Onecut (Oc) in photoreceptor cell formation is proposed throughout multicellular organisms. However, knowledge of the identity of the Oc downstream-acting factors that mediate specific tasks in the differentiation of the PRC remains limited. Here, we used transgenic perturbation of the Ciona robusta Oc protein to show its requirement for ciliary PRC differentiation. Then, transcriptome profiling between the trans-activation and trans-repression Oc phenotypes identified differentially expressed genes that are enriched in exocytosis, calcium homeostasis, and neurotransmission. Finally, comparison of RNA-Seq datasets in Ciona and mouse identifies a set of Oc downstream genes conserved between tunicates and vertebrates. The transcription factor Oc emerges as a key regulator of neurotransmission in retinal cell types.

Robust regulatory architecture of pan-neuronal gene expression

“…46,47 Encouragingly, a recent analysis of Ciona ONECUT revealed changes in gene expression of synaptic transmission molecules upon manipulation of ONECUT function in photoreceptor differentiation. 48 Another recent study revealed that ONECUT proteins can indeed induce neuronal features in a fibroblast-to-neuronal reprogramming approach in vitro. 49 Vertebrate ONECUT and CUX homologs are expressed in the nervous system, 46,47 but a systematic, comparative, and side-by-side analysis of all family members remains to be conducted to assess how broadly all family members cover the entire nervous system.…”

“…Decreased sensitivity to aldicarb correlates with a reduction in synaptic transmission. 48 Worms were tested every 30 min for paralysis by touching the head and tail three times each. The data are presented as the percentage of moving worms at the indicated time point; dots represent the mean of independent experiments for each genotype.…”

The Roles of Optogenetics and Technology in Neurobiology: A Review

“…By using the technology of optogenetics, the research of many difficult diseases has been advanced greatly. Using optogenetics to induce the differentiation of neural progenitor cells, the researchers were able to treat stroke in mice ( Yu et al, 2019 ; Peters et al, 2021 ; Vassalli et al, 2021 ). The mice were able to remove and reactivate a memory by changing the connections between related neurons in the brain with different frequencies of light ( Nabavi et al, 2014 ).…”

Robust regulatory architecture of pan-neuronal gene expression

“…A truly nervous system-wide analysis of the function of CUX or ONECUT genes in vertebrates has been missing; instead, several of vertebrate CUT or ONECUT homeodomain proteins have been well-studied in specific cellular contexts (Kropp and Gannon, 2016; Weiss and Nieto, 2019). Encouragingly, a recent analysis of Ciona ONECUT revealed changes in gene expression of synaptic transmission molecules upon manipulation of ONECUT function in photoreceptor differentiation (Vassalli et al, 2021). Our genetic loss of function analysis in C. elegans predicts that compound mutants may need to be generated in mice to assess CUT family function in vertebrate pan-neuronal gene expression.…”