Please cite this article in press as: Barber, B.A., et al., Dynamic expression of MEIS1 homeoprotein in E14.5 forebrain and differentiated forebrain-derived neural stem cells. Ann. Anatomy (2013), http://dx.doi.org/10.1016/j.aanat.2013.04.005 ARTICLE IN PRESS G Model AANAT-50792; No. of Pages 10 Annals of Anatomy xxx (2013) xxx–xxx Contents lists available at SciVerse ScienceDirect Annals of Anatomy j ourna l h omepage: www.elsevier.de/aanat Research article Dynamic expression of MEIS1 homeoprotein in E14.5 forebrain and differentiated forebrain-derived neural stem cells Benjamin A. Barber 1 , Vichithra R.B. Liyanage 1 , Robby M. Zachariah, Carl O. Olson, Melissa A.G. Bailey, Mojgan Rastegar ∗ Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada a r t i c l e i n f o Article history: Received 15 February 2013 Received in revised form 3 April 2013 Accepted 9 April 2013 Available online xxx Keywords: MEIS1 TALE gene expression E14.5 forebrain Neural stem cells Differentiation s u m m a r y Central nervous system development is controlled by highly conserved homeoprotein transcription fac- tors including HOX and TALE (Three Amino acid Loop Extension). TALE proteins are primarily known as HOX-cofactors and play key roles in cell proliferation, differentiation and organogenesis. MEIS1 is a TALE member with established expression in the developing central nervous system. MEIS1 is essential for embryonic development and Meis1 knockout mice dies at embryonic day (E) 14.5. However, Meis1/MEIS1 expression in the devolving forebrain, at this critical time-point has not been studied. Here, for the first time we characterize the region-specific expression of MEIS1 in E14.5 mouse forebrain, filling the gap of MEIS1 expression profile between E12.5 and E16.5. Previously, we reported MEIS1 transcriptional regu- latory role in neuronal differentiation and established forebrain-derived neural stem cells (NSC) for gene therapy application of neuronal genes. Here, we show the dynamic expression of Meis1/MEIS1 during the differentiation of forebrain-derived NSC toward a glial lineage. Our results show that Meis1/MEIS1 expression is induced during NSC differentiation and is expressed in both differentiated neurons and astrocytes. Confirming these results, we detected MEIS1 expression in primary cultures of in vivo dif- ferentiated cortical neurons and astrocytes. We further demonstrate Meis1/MEIS1 expression relative to other TALE family members in the forebrain-derived NSC in the absence of Hox genes. Our data provide evidence that forebrain-derived NSC can be used as an accessible in vitro model to study the expres- sion and function of TALE proteins, supporting their potential role in modulating NSC self-renewal and differentiation. © 2013 Elsevier GmbH. All rights reserved. 1. Introduction Highly conserved transcription factors of TALE (Three Amino acid Loop Extension) and HOX homeoproteins control central nervous system (CNS) development (Barber and Rastegar, 2010). TALE proteins are categorized into PBC/PBX and MEINOX/MEIS subfamilies and are involved in cell proliferation, differentiation, development, and organogenesis (Moens and Selleri, 2006). MEIS1 (Myeloid Ectopic viral Integration Site 1 homolog) belongs to the MEINOX/MEIS subfamily of TALE proteins and is essential for embryonic development and survival (Azcoitia et al., 2005; Hisa et al., 2004). MEIS1 misexpression is associated with various human ∗ Corresponding author at: Regenerative Medicine Program, Faculty of Medicine, Department of Biochemistry and Medical Genetics, University of Manitoba, 745 Ban- natyne Avenue, BMSB Rm. #627, Winnipeg, MB R3E 0J9, Canada. Tel.: +1 204 272 3108; fax: +1 204 789 3900. E-mail address: rastegar@cc.umanitoba.ca (M. Rastegar). 1 These authors contributed equally to this work. diseases including acute myeloid leukemia and acute lymphoblas- tic leukemia (Imamura et al., 2002; Lawrence et al., 1999), restless leg syndrome (Yang et al., 2011), and neuroblastoma (Geerts et al., 2003; Spieker et al., 2001). In neuroblastoma, MEIS1 is involved in cell differentiation and survival (Geerts et al., 2003; Spieker et al., 2001). During brain development, MEIS1 is expressed in the midbrain (Erickson et al., 2010; Heine et al., 2008) and hindbrain (Stedman et al., 2009). Previous reports on Meis1/MEIS1 expres- sion in developing forebrain describe its expression in E10.5–12.5 and E16.5 (Toresson et al., 2000a). However, its expression pattern in between E12.5 and E16.5 has not been shown previously, dur- ing which neurogenesis occurs followed by gliogenesis (Sanosaka et al., 2008). Studies in Meis1 knockout mouse models have shown that Meis1 knockout embryos survive only up to E14.5, highlight- ing the importance of MEIS1 expression at this stage of embryonic development (Hisa et al., 2004). Therefore, the first objective of this study was to characterize the Meis1/MEIS1 expression in E14.5 forebrain from where we isolated the neural stem cells (NSC), for a comprehensive understanding of MEIS1 expression profile dur- ing forebrain development. Further, we aimed to establish and 0940-9602/$ – see front matter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.aanat.2013.04.005