LIM-homeobox gene Lhx8 promote the differentiation of hippocampal newborn neurons into cholinergic neurons in vitro
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LIM-homeobox gene Lhx8 promote the differentiation of hippocampal newborn neurons into cholinergic neurons in vitro Peipei Zhu & Haoming Li & Guohua Jin & Meiling Tian & Xuefeng Tan & Jinhong Shi & Linqing Zou & Jianbing Qin
Received: 27 November 2012 / Accepted: 17 January 2013 / Published online: 6 February 2013 / Editor: T. Okamoto # The Society for In Vitro Biology 2013
Neurogenesis is a process by which newborn neurons are generated from neural stem cells or neural progenitor cells (NPCs). It is well known that the mammalian brain has the capacity to produce newborn neurons in two areas: the subventricular zone and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Newborn neurons from hippocampal NPCs in SGZ migrate a short distance into granule cells and establish synaptic connection with local neurons in vivo (Stanfield and Trice 1988; Cameron et al. 1993). Adult hippocampal neurogenesis is a multiple-step process and is regulated by many factors, both intrinsic and extrinsic. In addition to NPCs, astrocytes, endothelial cells, blood vessels, extracellular matrix, neurotransmitter systems, growth factors, neurotrophic factors, and many other components create a complex microenvironment to regulate neurogenesis (Vicario-Abejon et al. 2000; Doetsch 2003; WarnerSchmidt and Duman 2006; Balu and Lucki 2009). The generation of diverse neuronal phenotypes is also controlled by multiple extracellular and intracellular mechanisms operating in neuronal progenitors of postmitotic neurons. Homeobox genes as a kind of intrinsic factors govern cellular growth, differentiation, and migration and regulate some tissue-specific genes (Wilkinson 1989; Shashikant et al. 1991; Gehring 1992). LIM-homeobox P. Zhu : H. Li : G. Jin : M. Tian : X. Tan : J. Shi : L. Zou : J. Qin Department of Human Anatomy, Medical School of Nantong University, Nantong 226001, China G. Jin : J. Shi : L. Zou Department of Anatomy and Cytoneurobiology, Medical College of Soochow University, Suzhou 215123, China G. Jin (*) Nantong University, 19 Qixiu Road, Nantong 226001 Jiangsu, China e-mail: [email protected]
gene Lhx8 localized in the distal region of mouse chromosome 3, containing two tandemly repeated LIM motifs and a homeodomain. Lhx8 has a pivotal and specific role in the development and maintenance of basal forebrain cholinergic neurons (Kitanaka et al. 1998; Mori et al. 2004). Lhx8 and another LIM homeodomain protein Lhx6 regulated striatal neuronal precursor differentiation into cholinergic and GABAergic striatal interneurons (Fragkouli et al. 2009). In our previous report, overexpression of Lhx8 promoted the differentiation of hippocampal NPCs into cholinergic neurons on adherent conditions in vitro (Shi et al. 2012). However, several aspects of neuronal diversity, such as soma morphology, neurotransmitter phenotype, often become apparent after cell cycle exit and are controlled by the activity of members of homeobox family of transcription factors (Shirasaki and Pfaff 2002; Fragkouli et al. 2009). Adult hippocampal neurons
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