Scientific Online Resource System

Scripta Scientifica Medica

Expression of transcription factor Coup-TF1 (NR2F1) in developing occipital cortex in humans

Meglena Angelova, Radoslav Minkov, Vanya Goranova, Stoyan Pavlov, Vesselina Michaleva, Anton B. Tonchev


PURPOSES: We aimed to investigate the presence, distribution and abundance of transcription factor (TF) coup-tf1 (also known as NR2F1) in the germinative zones of human telencephalon during the fetal period. This transcription factor is of significance for the normal neuronal migration and differentiation of projection neurons in the mouse forebrain.

MATERIALS AND METHODS: Brain tissue samples from spontaneously aborted human fetuses aged between 12  and 28  gestational weeks (g.w.) were fixed in paraformaldehyde and histologically investigated. Sections immunostained for coup-tf1 were scanned and its expression in different zones of the occipital lobe of developing pallium was evaluated. COUP-TF1 positive cells were counted and their percentage of all DAPI-stained nuclei was calculated in order to establish the abundance of the COUP-TF1-expressing cells among the total cell population.

RESULTS: COUP-TF1 expression was prominent in all investigated zones of the developing human occipital lobe at stage 17 g.w. In all zones studied, COUP-TF1 positive cells presented a relatively high fraction (~71-95 %) of the cells counted with the highest value of 95.24% in the ventricular zone.

CONCLUSIONS: The present data on the location, abundance and distribution pattern of coup-tf1-expressing cells in the human occipital lobe provide information on the possibility that this TF might participate to human to corticogenesis, similarly to the mouse. 


COUP -TF1; NR2F1; cortical progenitors; human fetal telencephalon

Full Text


Ragsdale CW, Grove EA. Patterning the mammalian cerebral cortex. Curr Opin Neurobiol. 2001;11:50-8.

MuhChyi C, Juliandi B, Matsuda T, Nakashima K. Epigenetic regulation of neural stem cell fate during corticogenesis. Int J Dev Neurosci. 2013;31(6):424-33.

Sugiyama T, Wang JC, Scott DK, Granner DK. Transcription activation by the orphan nuclear receptor, chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI). Definition of the domain involved in the glucocorticoid response of the phosphoenolpyruvate carboxykinase gene. J Biol Chem. 2000;275(5):3446-54.

Yamaguchi H, Zhou C, Lin SC, Durand B, Tsai SY, Tsai MJ. The nuclear orphan receptor COUP-TFI is important for differentiation of oligodendrocytes. Dev Biol. 2004;266(2):238-51.

Wang L, Shiraki A, Itahashi M, Akane H, Abe H, Mitsumori K et al. Aberration in epigenetic gene regulation in hippocampal neurogenesis by developmental exposure to manganese chloride in mice. Toxicol Sci. 2013;136(1):154-65.

Pereira FA, Tsai MJ, Tsai SY. COUP-TF orphan nuclear receptors in development and differentiation. Cell Mol Life Sci. 2000;57(10):1388-98.

Zhuang Y, Gudas LJ. Overexpression of COUP-TF1 in murine embryonic stem cells reduces retinoic acid-associated growth arrest and increases extraembryonic endoderm gene expression. Differentiation. 2008;76(7):760-71.

Ben-Shushan E, Sharir H, Pikarsky E, Bergman Y. A dynamic balance between ARP-1/COUP-TFII, EAR-3/COUP-TFI, and retinoic acid receptor:retinoid X receptor heterodimers regulates Oct-3/4 expression in embryonal carcinoma cells. Mol Cell Biol. 1995;15(2):1034-48.

Zhou C, Tsai SY, Tsai MJ. COUP-TFI: an intrinsic factor for early regionalization of the neocortex. Genes Dev. 2001;15(16):2054-9.

Borello U, Madhavan M, Vilinsky I, Faedo A, Pierani A, Rubenstein J et al. Sp8 and COUP-TF1 reciprocally regulate patterning and Fgf signaling in cortical progenitors. Cereb Cortex. 2014;24(6):1409-21.

Alfano C, Viola L, Heng JI, Pirozzi M, Clarkson M, Flore G, et al. COUP-TFI promotes radial migration and proper morphology of callosal projection neurons by repressing Rnd2 expression. Development. 2011;138(21):4685-97.

Piñon MC, Tuoc TC, Ashery-Padan R, Molnár Z, Stoykova A. Altered molecular regionalization and normal thalamocortical connections in cortex-specific Pax6 knock-out mice. J Neurosci. 2008;28(35):8724-34.

Armentano M, Chou SJ, Tomassy GS, Leingärtner A, O`Leary DDM, Studer M. COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas. Nat Neurosci. 2007;10:1277-86.

Faedo A, Tomassy GS, Ruan Y, Teichmann H, Krauss S, Pleasure SJ et al. COUP-TF1 coordinates cortical patterning, neurogenesis, and laminar fate and modulates MAPK/ERK, AKT and beta-catenin signaling. Cereb Cortex. 2008;18(9):2117-31.

About The Authors

Meglena Angelova
Medical University of Varna

Department of Anatomy, Histology and Embryology

Radoslav Minkov
Medical University of Varna

University Hospital `Prof. Stamatov` - Varna, Bulgaria

Vanya Goranova
Medical University of Varna

Department of Anatomy, Histology and Embryology

Stoyan Pavlov
Medical University of Varna

Department of Anatomy, Histology and Embryology

Vesselina Michaleva
Medical University of Varna

Anton B. Tonchev
Medical University of Varna

Department of Anatomy, Histology and Embryology

Font Size