Lhx2 Selector Activity Specifies Cortical Identity and Suppresses Hippocampal Organizer Fate

Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
Science (Impact Factor: 33.61). 02/2008; 319(5861):304-9. DOI: 10.1126/science.1151695
Source: PubMed


The earliest step in creating the cerebral cortex is the specification of neuroepithelium to a cortical fate. Using mouse genetic mosaics and timed inactivations, we demonstrated that Lhx2 acts as a classic selector gene and essential intrinsic determinant of cortical identity. Lhx2 selector activity is restricted to an early critical period when stem cells comprise the cortical neuroepithelium, where it acts cell-autonomously to specify cortical identity and suppress alternative fates in a spatially dependent manner. Laterally, Lhx2 null cells adopt antihem identity, whereas medially they become cortical hem cells, which can induce and organize ectopic hippocampal fields. In addition to providing functional evidence for Lhx2 selector activity, these findings show that the cortical hem is a hippocampal organizer.

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Available from: Satyaki Prasad Rajavasireddy, Feb 19, 2014
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    • "Cortical areas and cortical folds form during embryonic development from the cortical anlage in highly stereotyped patterns, suggesting a strong genetic regulation (Borrell & Reillo, 2012). A limited number of transcription factors have been identified to control the size, position, and area identities of cortical subdivisions, including Pax6, Lhx2, Emx2, and Sp8 (Bishop et al, 2000; Yun et al, 2001; Sahara et al, 2007; Mangale et al, 2008; Chou et al, 2009). Despite the subdivision of the mature cerebral cortex into discrete structural/functional units, these transcription factors controlling regional fate are expressed in gradients across such subdivisions in the embryonic cortical germinal layers, raising the question of how the latter are implemented. "
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    • "Data are from mouse (E9.5–12.5) and chick (E4–E8) expression studies of mouse: Emx1/2, Pax6, Ngn2, Dlx2, Sommer et al. (1996), Puelles et al. (2000), Yun et al. (2001), Muzio et al. (2002), Backman et al. (2005); Wnt3a, Wnt8b, Bmp4, Foxg1, Parr et al. (1993), Hanashima et al. (2007); Lhx2, Monuki et al. (2001), Chou et al. (2009), Mangale et al. (2008); Dbx1, Medina et al. (2004), Bielle et al. (2005); Sfrp2, Kim et al. (2001), and chick: Emx1/2, Lhx2, Pax6, Dlx2, von Frowein et al. (2006), Puelles et al. (2000); Foxg1, Bell et al. (2001); Ngn2, Sfrp1, von Frowein et al. (2002); Wnt8b, Garda et al., 2002. In mouse, the expression of Emx1, Emx2 and Ngn2 extends into the Wnt3a + medial pallium domain. "
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    • "However, at later stages, LHX2 regulates the cell fate decisions of hippocampal progenitors. Downregulation of Lhx2 in the embryonic hippocampus was found to promote astrogliogenesis at the expense of neurogenesis, and overexpression of Lhx suppressed GFAP promoter activity, thereby favoring neuronal differentiation (Mangale et al., 2008). "
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