Papers by Nicholas Genethliou
Biochemical and Biophysical Research Communications, 2009
During ventral spinal cord (vSC) development, the p3 and pMN progenitor domain boundary is though... more During ventral spinal cord (vSC) development, the p3 and pMN progenitor domain boundary is thought to be maintained by cross-repressive interactions between NKX2.2 and PAX6. Using loss-of-function analysis during the neuron-glial fate switch we show that the identity of the p3 domain is not maintained by the repressive function of NKX2.2 on Pax6 expression, even in the absence of NKX2.9. We further show that NKX2.2 is necessary to induce the expression of Slit1 and Sulfatase 1 (Sulf1) in the vSC in a PAX6independent manner. Conversely, we show that PAX6 regulates Sulf1/Slit1 expression in the vSC in an NKX2.2/NKX6.1-independent manner. Consequently, deregulation of Sulf1 expression in Pax6-mutant embryos has stage-specific implications on neural patterning, associated with enhancement of Sonic Hedgehog activity. On the other hand, deregulation of Slit1 expression in gliogenic neural progenitors leads to changes in Astrocyte subtype identity. These data provide important insights into specific functions of PAX6 and NKX2.2 during glial cell specification that have so far remained largely unexplored.
Small Ruminant Research, 2010
... 92 (2008), pp. 773776. Tantia et al., 2006 MS Tantia, RK Vijh, BP Mishra, B. Mishra, ST Kuma... more ... 92 (2008), pp. 773776. Tantia et al., 2006 MS Tantia, RK Vijh, BP Mishra, B. Mishra, ST Kumar and M. Sodhi, DGAT1 and ABCG2 polymorphism in Indian cattle (Bos indicus) andbuffalo (Bubalus bubalis) breeds, BMC Vet. Res. 2 (2006), p. 32. ...
Biochemical and Biophysical Research Communications, 2009
The ATP-binding cassette (ABC) transporter 2 (ABCG2) is expressed by stem cells in many organs an... more The ATP-binding cassette (ABC) transporter 2 (ABCG2) is expressed by stem cells in many organs and in stem cells of solid tumors. These cells are isolated based on the side population (SP) phenotype, a Hoechst 3342 dye efflux property believed to be conferred by ABCG2. Because of the limitations of this approach we generated transgenic mice that express Nuclear GFP (GFPn) coupled to the Puromycin-resistance gene, under the control of ABCG2 promoter/enhancer sequences. We show that ABCG2 is expressed in neural progenitors of the developing forebrain and spinal cord and in embryonic and adult endothelial cells of the brain. Using the neurosphere assay, we isolated tripotent ABCG2-expressing neural stem cells from embryonic mouse brain. This transgenic line is a powerful tool for studying the expression of ABCG2 in many tissues and for performing functional studies in different experimental settings.
Biochemical and Biophysical Research Communications, 2009
During neural development the transition from neurogenesis to gliogenesis, known as the neuron-gl... more During neural development the transition from neurogenesis to gliogenesis, known as the neuron-glial (N/G) fate switch, requires the coordinated function of patterning factors, pro-glial factors and Notch signalling. How this process is coordinated in the embryonic spinal cord is poorly understood. Here, we demonstrate that during the N/G fate switch in the ventral spinal cord (vSC) SOX1 links the function of neural patterning and Notch signalling. We show that, SOX1 expression in the vSC is regulated by PAX6, NKX2.2 and Notch signalling in a domain-specific manner. We further show that SOX1 regulates the expression of Hes1 and that loss of Sox1 leads to enhanced production of oligodendrocyte precursors from the pMN. Finally, we show that Notch signalling functions upstream of SOX1 during this fate switch and is independently required for the acquisition of the glial fate per se by regulating Nuclear Factor I A expression in a PAX6/SOX1/HES1/HES5-independent manner. These data integrate functional roles of neural patterning factors, Notch signalling and SOX1 during gliogenesis.
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Papers by Nicholas Genethliou