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The Journal of Neuroscience, September 17, 2008, 28(38):9504-9518; doi:10.1523/JNEUROSCI.2341-08.2008

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Development/Plasticity/Repair
Molecular Specification and Patterning of Progenitor Cells in the Lateral and Medial Ganglionic Eminences

Eric S. Tucker,^1,4 Samantha Segall,^3 * Deepak Gopalakrishna,^3 * Yongqin Wu,⁴ Mike Vernon,⁴ Franck Polleux,^2,4 and Anthony-Samuel LaMantia^1,4

¹Departments of Cell and Molecular Physiology and ²Pharmacology, ³Curriculum of Genetics and Molecular Biology, and ⁴University of North Carolina Neuroscience Center, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina 27599

Correspondence should be addressed to Dr. Anthony-Samuel LaMantia, Department of Cell and Molecular Physiology, Campus Box 7545, Chapel Hill, NC 27599. Email: anthony_lamantia{at}med.unc.edu

We characterized intrinsic and extrinsic specification of progenitors in the lateral and medial ganglionic eminences (LGE and MGE). We identified seven genes whose expression is enriched or restricted in either the LGE [biregional cell adhesion molecule-related/downregulated by oncogenes binding protein (Boc), Frizzled homolog 8 (Fzd8), Ankrd43 (ankyrin repeat domain-containing protein 43), and Ikzf1 (Ikaros family zinc finger 1)] or MGE [Map3k12 binding inhibitory protein 1 (Mbip); zinc-finger, SWIM domain containing 5 (Zswim5); and Adamts5 [a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 5]]. Boc, Fzd8, Mbip, and Zswim5 are apparently expressed in LGE or MGE progenitors, whereas the remaining three are seen in the postmitotic mantle zone. Relative expression levels are altered and regional distinctions are lost for each gene in LGE or MGE cells propagated as neurospheres, indicating that these newly identified molecular characteristics of LGE or MGE progenitors depend on forebrain signals not available in the neurosphere assay. Analyses of Pax6^Sey/Sey, Shh^–/–, and Gli3^XtJ/XtJ mutants suggests that LGE and MGE progenitor identity does not rely exclusively on previously established forebrain-intrinsic patterning mechanisms. Among a limited number of additional potential patterning mechanisms, we found that extrinsic signals from the frontonasal mesenchyme are essential for Shh- and Fgf8-dependent regulation of LGE and MGE genes. Thus, extrinsic and intrinsic forebrain patterning mechanisms cooperate to establish LGE and MGE progenitor identity, and presumably their capacities to generate distinct classes of neuronal progeny.

Key words: forebrain; development; induction; interneuron; cell fate; explant; diversity; microarray

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Received May 21, 2008; revised Aug. 5, 2008; accepted Aug. 8, 2008.

Correspondence should be addressed to Dr. Anthony-Samuel LaMantia, Department of Cell and Molecular Physiology, Campus Box 7545, Chapel Hill, NC 27599. Email: anthony_lamantia{at}med.unc.edu

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