Identification of a<i>Pax6</i>-Dependent Epidermal Growth Factor Family Signaling Source at the Lateral Edge of the Embryonic Cerebral Cortex

178

The amygdaloid complex is a group of nuclei that are thought to originate from multiple sites of the dorsal and ventral telencephalic neuroepithelium. The mechanisms that regulate their development are essentially unknown. We studied the role of Pax6 and Emx2, two transcription factors that regulate regional specification and growth of the telencephalon, in the morphogenesis of the amygdaloid complex. We used a set of specific marker genes that identify distinct amygdaloid nuclei to analyze Pax6/Small eye and Emx2 knock-out mutant mouse brains. We found that there is a selective requirement for Pax6, but not Emx2, in the formation a subset of nuclei within the amygdaloid complex. Specifically, structures that were not previously considered to be developmentally linked, the nucleus of the lateral olfactory tract and the lateral, basolateral, and basomedial nuclei, all appear to have a common requirement for Pax6. Together, our findings provide new insights into the origins and mechanisms underlying the development of the amygdaloid complex.

Section: Discussionmentioning

confidence: 99%

Selective Requirement of Pax6, But Not Emx2, in the Specification and Development of Several Nuclei of the Amygdaloid Complex

Tole¹,

Remedios²,

Saha³

et al. 2005

178

“…Furthermore, the CGE also contains the caudal prolongations of the pallial territories that are also found rostrally in the most dorsal aspect of the LGE and immediately adjacent to it. These pallial components are characterized by the expression of Dbx1, Fgf7, Sfrp2, and Pax6 (and several other markers) and the lack of Emx1 at early development stages (Smith-Fernández et al, 1998;Puelles et al, 2000;Kim et al, 2001;Assimacopoulos et al, 2003;Medina et al, 2004). Because pallial, LGE, and MGE domains are organized concentrically in the telencephalic hemispheres (Puelles et al, 2000), the CGE contains progressively less progenitor pools as it extends caudally, until eventually the most caudal CGE appears to only consist of pallial progenitors (Kim et al, 2001, their Fig.…”

Section: The Cge Contains the Caudal Extension Of Lge And Mge Progenimentioning

confidence: 99%

Delineation of Multiple Subpallial Progenitor Domains by the Combinatorial Expression of Transcriptional Codes

Flames¹,

Pla²,

Gelman³

et al. 2007

520

792

The mammalian telencephalon is considered the most complex of all biological structures. It comprises a large number of functionally and morphologically distinct types of neurons that coordinately control most aspects of cognition and behavior. The subpallium, for example, not only gives rise to multiple neuronal types that form the basal ganglia and parts of the amygdala and septum but also is the origin of an astonishing diversity of cortical interneurons. Despite our detailed knowledge on the molecular, morphological, and physiological properties of most of these neuronal populations, the mechanisms underlying their generation are still poorly understood. Here, we comprehensively analyzed the expression patterns of several transcription factors in the ventricular zone of the developing subpallium in the mouse to generate a detailed molecular map of the different progenitor domains present in this region. Our study demonstrates that the ventricular zone of the mouse subpallium contains at least 18 domains that are uniquely defined by the combinatorial expression of several transcription factors. Furthermore, the results of microtransplantation experiments in vivo corroborate that anatomically defined regions of the mouse subpallium, such as the medial ganglionic eminence, can be subdivided into functionally distinct domains.

“…During embryogenesis, cells of the LCS emerge from the "molecular" corticostriatal border (CSB), the region of the dorsal LGE (dLGE) in which pallial gene expression [e.g., Pax6 (paired box gene 6) and Ngn2 (neurogenin homolog 2)] abuts subpallial gene expression [e.g., Gsh2 (genomic screened homeobox 2) and Dlx1/2 (distal-less homeobox 2) (for review, see Corbin et al, 2001; Molnár and Butler, 2002)]. This "molecular" CSB (herein referred to as CSB) is po-sitioned just ventral to the corticostriatal sulcus and also is the site of expression of a variety of specific intrinsic [e.g., Dbx1 (developing brain homeobox 1), Er81 (Ets transcription factor ER81), Sp8 (a member of the Sp1 zinc finger transcription factor gene family), and Tsh1 (Teashirt 1)] and extrinsic [e.g., Sfrp2 (secreted frizzled-related protein 2), Tgf-␣, and Fgf7] factors (Lu et al, 1996;Kim et al, 2001;Assimacopoulos et al, 2003;Stenman et al, 2003a;Caubit et al, 2005;Waclaw et al, 2006). Furthermore, gene expression studies have indicated that the LCS consists of at least two progenitor populations that arise from both the pallial and subpallial compartments (Stoykova et al, 1996;Puelles et al, 2000;Toresson et al, 2000;Yun et al, 2001;Medina et al, 2004;Tole et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Cell Migration along the Lateral Cortical Stream to the Developing Basal Telencephalic Limbic System

Carney¹,

Alfonso²,

Cohen³

et al. 2006

113

During embryogenesis, the lateral cortical stream (LCS) emerges from the corticostriatal border (CSB), the boundary between the developing cerebral cortex and striatum. The LCS is comprised of a mix of pallial-and subpallial-derived neural progenitor cells that migrate to the developing structures of the basal telencephalon, most notably the piriform cortex and amygdala. Using a combination of in vitro and in vivo approaches, we analyzed the timing, composition, migratory modes, origin, and requirement of the homeodomaincontaining transcription factor Gsh2 (genomic screened homeobox 2) in the development of this prominent migratory stream. We reveal that Pax6 (paired box gene 6)-positive pallial-derived and Dlx2 (distal-less homeobox 2)-positive subpallial-derived subpopulations of LCS cells are generated in distinct temporal windows during embryogenesis. Furthermore, our data indicate the CSB border not only is comprised of separate populations of pallial-and subpallial-derived progenitors that contribute to the LCS but also a subpopulation of cells coexpressing Pax6 and Dlx2. Moreover, despite migrating along a route outlined by a cascade of radial glia, the Dlx2-positive population appears to migrate primarily in an apparent chain-like manner, with LCS migratory cells being generated locally at the CSB with little contribution from other subpallial structures such as the medial, lateral, or caudal ganglionic eminences. We further demonstrate that the generation of the LCS is dependent on the homeodomain-containing gene Gsh2, revealing a novel requirement for Gsh2 in telencephalic development.