Pax6 Is Required at the Telencephalic Pallial-Subpallial Boundary for the Generation of Neuronal Diversity in the Postnatal Limbic System

Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 04/2011; 31(14):5313-24. DOI: 10.1523/JNEUROSCI.3867-10.2011
Source: PubMed


During embryogenesis, the pallial-subpallial boundary (PSB) divides the two main progenitor domains in the telencephalon: the pallium, the major source of excitatory neurons, and the subpallium, the major source of inhibitory neurons. The PSB is formed at the molecular interface between the pallial (high Pax6+) and subpallial (high Gsx2+) ventricular zone (VZ) compartments. Initially, the PSB contains cells that express both Pax6 and Gsx2, but during later stages of development this boundary is largely refined into two separate compartments. In this study we examined the developmental mechanisms underlying PSB boundary formation and the postnatal consequences of conditional loss of Pax6 function at the PSB on neuronal fate in the amygdala and olfactory bulb, two targets of PSB-derived migratory populations. Our cell fate and time-lapse imaging analyses reveal that the sorting of Pax6+ and Gsx2+ progenitors during embryogenesis is the result of a combination of changes in gene expression and cell movements. Interestingly, we find that in addition to giving rise to inhibitory neurons in the amygdala and olfactory bulb, Gsx2+ progenitors generate a subpopulation of amygdala excitatory neurons. Consistent with this finding, targeted conditional ablation of Pax6 in Gsx2+ progenitors results in discrete local embryonic patterning defects that are linked to changes in the generation of subsets of postnatal excitatory and inhibitory neurons in the amygdala and inhibitory neurons in the olfactory bulb. Thus, in PSB progenitors, Pax6 plays an important role in the generation of multiple subtypes of neurons that contribute to the amygdala and olfactory bulb.

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    • "signaling induces the antihem , and is strongly expressed in the ventral pallium and equatorial aspect of the hemisphere , showing a gradient of activity from the anterolateral to the caudomedial hemisphere . Pax6 is required for the development of lateral and ventral pallial identities ( olfactory and amygdalar components ; Piñon et al . , 2008 ; Cocas et al . , 2011 ) , and patterns the anterolateral neocortex ( Bishop et al . , 2000 ) . Pax6 is a critical promotor of progenitor proliferation , and an essential component for the evolutionary expansion of the neocortex ( Poluch and Juliano , 2015 ) . The developmental expression pattern of signaling factors is mostly conserved between chick and mous"
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    ABSTRACT: Together with a complex variety of behavioral, physiological, morphological, and neurobiological innovations, mammals are characterized by the development of an extensive isocortex (also called neocortex) that is both laminated and radially organized, as opposed to the brain of birds and reptiles. In this article, we will advance a developmental hypothesis in which the mechanisms of evolutionary brain growth remain partly conserved across amniotes (mammals, reptiles and birds), all based on Pax6 signaling or related morphogens. Despite this conservatism, only in mammals there is an additional upregulation of dorsal and anterior signaling centers (the cortical hem and the anterior forebrain, respectively) that promoted a laminar and a columnar structure into the neocortex. It is possible that independently, some birds also developed an upregulated dorsal pallium.
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    • "Furthermore , Pax6 specifies the antihem, which is coextensive with the ventral pallium and secretes EGFs, FGFs and frizzled-related proteins (FRPs) that counteract the influence of dorsal signals like Wnts (Assimacopoulos et al., 2003). Pax6 and the antihem participate in the differentiation of pallial amygdalar structures (Cocas et al., 2011), and Pax6 is required for proper development of both ventral and dorsal pallial structures in mammals (for more detailed reviews involving these and additional regulatory systems see Hoch et al., 2009; Medina and Abellán, 2009; Medina et al., 2011, and Alfano and Studer, 2013). "
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    • "The migratory cells of the lateral cortical stream (LCS) are derived from progenitors in the VZ of the PSPB and migrate ventrally towards the amygdaloid region where they contribute to the developing amygdala [47,50,59,60]. The LCS contains cells derived from both the pallium (Pax6+ and Tbr1+) and the subpallium (Dlx2+ and Gsh2+) [47,50,59]. Tau-GFP labels a set of Pax6-expressing cells which appear to be migrating towards the basolateral telencephalon of our PAX6 YAC transgenic lines at both E12.5 and E15.5. "
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