Protooncogene Ski cooperates with the chromatin-remodeling factor Satb2 in specifying callosal neurons

Abstract

First insights into the molecular programs orchestrating the progression from neural stem cells to cortical projection neurons are emerging. Loss of the transcriptional regulator Ski has been linked to the human 1p36 deletion syndrome, which includes central nervous system defects. Here, we report critical roles for Ski in the maintenance of the neural stem cell pool and the specification of callosal neurons. Ski -deficient callosal neurons lose their identity and ectopically express the transcription factor Ctip2. The misspecified callosal neurons largely fail to form the corpus callosum and instead redirect their axons toward subcortical targets. We identify the chromatin-remodeling factor Satb2 as a partner of Ski, and show that both proteins are required for transcriptional repression of Ctip2 in callosal neurons. We propose a model in which Satb2 recruits Ski to the Ctip2 locus, and Ski attracts histone deacetylases, thereby enabling the formation of a functional nucleosome remodeling and deacetylase repressor complex. Our findings establish a central role for Ski–Satb2 interactions in regulating transcriptional mechanisms of callosal neuron specification.

Further delineation of the SATB2 phenotype

“…24,34,35 In the mammalian cerebral cortex, neurons can be divided into two major classes: cortico-cortical projection neurons, which are concentrated in the upper layers of the cortex, and subcortical projection neurons, which are found in the deep layers. Early progenitor cells in the ventricular zone give rise to deep layer neurons while progenitors in the subventricular zone give rise to upper layer neurons.…”

Upregulation of Ski in Fibroblast is Implicated in the Peroxisome Proliferator- Activated Receptor d-Mediated Wound Healing

“…As a versatile transcriptional regulator, it modulates multiple gene expression and is involved in many physiological and pathological processes [6][7][8][9]. However, the transcriptional or translational modulation of Ski gene in these conditions is not clear.…”

The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone‐Induced Central Nervous System Demyelination

“…Such increase might contribute to counteract the exacerbated demyelination observed after CPZ dietary combined with 1 mg/kg of WIN. In line with these findings, it is described that neurons for Ski‐deficient mice lose their identity and cannot culminate to form the corpus callosum 46.…”