Godwin Sokpor

Menu Options
Godwin Sokpor
Position PhD Student
Tel. +49-(0)551/39-33900


    • 2018
    • Epigenetic regulation by BAF (mSWI/SNF) complexes limits neural stem cell proliferation by suppressing Wnt signaling in late embryonic development.
      Nguyen H*, Kerimoglu C*, Pirouz M, Pham L, Kiszka KA, Sokpor G, Sakib MS, Rosenbusch J, Teichmann U, Seong RH, Stoykova A, Fischer A, Staiger JF, Tuoc T .
      Stem Cell Reports, doi: 10.1016/j.stemcr.2018.04.014, 2018.
      abstract link

      During early cortical development, neural stem cells (NSCs) divide symmetrically to expand the progenitor pool, whereas in later stages, NSCs divide asymmetrically to self-renew and produce other cell types. The timely switch from such proliferative to differentiative division critically determines progenitor and neuron numbers. However, the mechanisms that limit proliferative division in late cortical development are not fully understood. Here, we show that the BAF (mSWI/SNF) complexes restrict proliferative competence and promote neuronal differentiation in late corticogenesis. Inactivation of BAF complexes leads to H3K27me3-linked silencing of neuronal differentiation-related genes, with concurrent H3K4me2-mediated activation of proliferation-associated genes via de-repression of Wnt signaling. Notably, the deletion of BAF complexes increased proliferation of neuroepithelial cell-like NSCs, impaired neuronal differentiation and exerted a Wnt-dependent effect on neocortical and hippocampal development. Thus, these results demonstrate that BAF complexes act as both activators and repressors to control global epigenetic and gene expression programs in late corticogenesis.

    • ATP-dependent chromatin remodeling during cortical neurogenesis.
      Sokpor G*, Hernandez RC*, Rosenbusch J, Staiger JF, Tuoc T.
      Front. Neurosci. | doi: 10.3389/fnins.2018.00226 , 2018.
      abstract link

      The generation of individual neurons (neurogenesis) during cortical development occurs in discrete steps that are subtly regulated and orchestrated to ensure normal histogenesis and function of the cortex. Notably, various gene expression programs are known to critically drive many facets of neurogenesis with a high level of specificity during brain development. Typically, precise regulation of gene expression patterns ensures that key events like proliferation and differentiation of neural progenitors, specification of neuronal subtypes, as well as migration and maturation of neurons in the developing cortex occur properly. ATP-dependent chromatin remodeling complexes regulate gene expression through utilization of energy from ATP hydrolysis to reorganize chromatin structure. These chromatin remodeling complexes are characteristically multimeric, with some capable of adopting functionally distinct conformations via subunit reconstitution to perform specific roles in major aspects of cortical neurogenesis. In this review, we highlight the functions of such chromatin remodelers during cortical development. We also bring together various proposed mechanisms by which ATP-dependent chromatin remodelers function individually or in concert, to specifically modulate vital steps in cortical neurogenesis.

    • Transcriptional and epigenetic control of mammalian olfactory epithelium development.
      Sokpor G*, Abbas E*, Rosenbusch J, Staiger JF, Tuoc T..
      Molecular Neurobiology (https://doi.org/10.1007/s12035-018-0987-y), 2018.
      abstract link

      The postnatal mammalian olfactory epithelium (OE) represents a major aspect of the peripheral olfactory system. It is a pseudostratified tissue that originates from the olfactory placode and is composed of diverse cells, some of which are specialized receptor neurons capable of transducing odorant stimuli to afford the perception of smell (olfaction). The OE is known to offer a tractable miniature model for studying the systematic generation of neurons and glia that typify neural tissue development. During OE development, stem/progenitor cells that will become olfactory sensory neurons and/or non-neuronal cell types, display fine spatiotemporal expression of neuronal and non-neuronal genes that ensures their proper proliferation, differentiation, survival, and regeneration. Many factors, including transcription and epigenetic factors have been identified as key regulators of the expression of such requisite genes to permit normal OE morphogenesis. Typically, specific interactive regulatory networks established between transcription and epigenetic factors/cofactors orchestrate histogenesis in the embryonic and adult OE. Hence, investigation of these regulatory networks critical for OE development promises to disclose strategies that may be employed in manipulating the stepwise transition of olfactory precursor cells to become fully differentiated and functional neuronal and non-neuronal cell types. Such strategies potentially offer formidable means of replacing injured or degenerated neural cells as therapeutics for nervous system perturbations. This review recapitulates the developmental cellular diversity of the olfactory neuroepithelium and discusses findings on how the precise and cooperative molecular control by transcriptional and epigenetic machinery is indispensable for OE ontogeny.

    • 2017
    • Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders.
      Sokpor G*, Xie Y*, Rosenbusch J, Tuoc T.
      Front. Mol. Neurosci. | doi: 10.3389/fnmol.2017.00243 , 2017.
      abstract link

      The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra’s syndrome spectrum, Hirschsprung’s disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders.

    • 2016
    • mSWI/SNF (BAF) complexes are indispensable for the neurogenesis and development of embryonic olfactory epithelium.
      Bachmann C*, Nguyen H*, Rosenbusch J*, Pham L, Rabe T, Patwa M, Sokpor G, Seong RH, Ashery-Padan R, Mansouri A, Stoykova A, Staiger JF, Tuoc T..
      Plos Genetics, 2016. 12(9), *equally contributed authors
      abstract link

      Neurogenesis is a key developmental event through which neurons are generated from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes have been reported to play essential roles in the neurogenesis of the central nervous system. However, whether BAF complexes are required for neuron generation in the olfactory system is unknown. Here, we identified onscBAF and ornBAF complexes, which are specifically present in olfactory neural stem cells (oNSCs) and olfactory receptor neurons (ORNs), respectively. We demonstrated that BAF155 subunit is highly expressed in both oNSCs and ORNs, whereas high expression of BAF170 subunit is observed only in ORNs. We report that conditional deletion of BAF155, a core subunit in both onscBAF and ornBAF complexes, causes impaired proliferation of oNSCs as well as defective maturation and axonogenesis of ORNs in the developing olfactory epithelium (OE), while the high expression of BAF170 is important for maturation of ORNs. Interestingly, in the absence of BAF complexes in BAF155/BAF170 double-conditional knockout mice (dcKO), OE is not specified. Mechanistically, BAF complex is required for normal activation of Pax6-dependent transcriptional activity in stem cells/progenitors of the OE. Our findings unveil a novel mechanism mediated by the mSWI/SNF complex in OE neurogenesis and development.

    • Epigenetic regulation by BAF (mSWI/SNF) chromatin remodeling complexes is indispensable for embryonic development.
      Nguyen H*, Sokpor G*, Pham L, Rosenbusch J, Stoykova A, Staiger JF, Tuoc T.
      Cell Cycle, 2016. 2016, 18;15(10):1317-24, equally contributed authors
      abstract link

      The multi-subunit chromatin-remodeling SWI/SNF (known as BAF for Brg/Brm-associated factor) complexes play essential roles in development. Studies have shown that the loss of individual BAF subunits often affects local chromatin structure and specific transcriptional programs. However, we do not fully understand how BAF complexes function in development because no animal mutant had been engineered to lack entire multi-subunit BAF complexes. Importantly, we recently reported that double conditional knock-out (dcKO) of the BAF155 and BAF170 core subunits in mice abolished the presence of the other BAF subunits in the developing cortex. The generated dcKO mutant provides a novel and powerful tool for investigating how entire BAF complexes affect cortical development. Using this model, we found that BAF complexes globally control the key heterochromatin marks, H3K27me2 and -3, by directly modulating the enzymatic activity of the H3K27 demethylases, Utx and Jmjd3. Here, we present further insights into how the scaffolding ability of the BAF155 and BAF170 core subunits maintains the stability of BAF complexes in the forebrain and throughout the embryo during development. Furthermore, we show that the loss of BAF complexes in the above-described model up-regulates H3K27me3 and impairs forebrain development and embryogenesis. These findings improve our understanding of epigenetic mechanisms and their modulation by the chromatin-remodeling SWI/SNF complexes that control embryonic development.