Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala

Center for Neuroscience Research, Children's National Medical Center, 111 Michigan Avenue, NW, Suite 645, Washington, DC 20010, USA.
Nature Neuroscience (Impact Factor: 16.1). 02/2009; 12(2):141-9. DOI: 10.1038/nn.2241
Source: PubMed


The development of the amygdala, a central structure of the limbic system, remains poorly understood. We found that two spatially distinct and early-specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature mouse amygdala. We found that Dbx1-positive cells of the ventral pallium generate the excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a previously unknown migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1-positive, POA-derived population migrated specifically to the amygdala and, as defined by both immunochemical and electrophysiological criteria, generated a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a previously unknown progenitor pool dedicated to the limbic system.

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    • "The VPall migratory stream and associated glial bundle (Medina et al., 2004 ) is strictly eschewed by all claustral and migrated dorsal endopiriform Nr4a2-positive cells developing initially within the LPall. We already know that the VPall stream does not practically contribute neurons to either the claustrum or the insula, as demonstrated by Dbx1-derived progeny (Figure 4.10C; Bielle et al., 2005; Hirata et al., 2002 Hirata et al., , 2009 Teissier et al., 2010). There are nevertheless ventropallial Dbx1-derived Cajal-Retzius neurons that pass subpially across LPall into the DPall (Figure 4.16; Bielle et al., 2005), some of which probably remain in the layer 1 of the insula. "
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    Full-text · Chapter · Dec 2014
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    • "We used mice that express Cre recombinase fused to the tamoxifen-sensitive estrogen receptor (CreER T2 ) in cells expressing Dbx1, that is, Dbx1 CreERT2 (Hirata et al. 2009). Dbx1 CreERT2 mice were mated with floxed reporter mice in which the Rosa26 locus was modified by targeted insertion of a loxP-flanked STOP cassette followed by tandem dimer (td) Tomato (Rosa26 tdTomato , strain name: B6;129S6-Gt(ROSA)26Sor tm9(CAG-tdTomato)Hze /J, Jax No. 007905; Madisen et al. 2010). "
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    ABSTRACT: Inspiratory active pre-Bötzinger complex (preBötC) networks produce the neural rhythm that initiates and controls breathing movements. We previously identified the preBötC in the newborn rat brainstem and established anatomically defined transverse slices in which the preBötC remains active when exposed at one surface. This follow-up study uses a neonatal mouse model in which the preBötC as well as a genetically defined class of respiratory interneurons can be identified and selectively targeted for physiological recordings. The population of glutamatergic interneurons whose precursors express the transcription factor Dbx1 putatively comprises the core respiratory rhythmogenic circuit. Here, we used intersectional mouse genetics to identify the brainstem distribution of Dbx1-derived neurons in the context of observable respiratory marker structures. This reference brainstem atlas enabled online histology for generating calibrated sandwich slices to identify the preBötC location, which was heretofore unspecified for perinatal mice. Sensitivity to opioids ensured that slice rhythms originated from preBötC neurons and not parafacial respiratory group/retrotrapezoid nucleus (pFRG/RTN) cells because opioids depress preBötC, but not pFRG/RTN rhythms. We found that the preBötC is centered ~0.4 mm caudal to the facial motor nucleus in this Cre/lox reporter mouse during postnatal days 0–4. Our findings provide the essential basis for future optically guided electrophysiological and fluorescence imaging-based studies, as well as the application of other Cre-dependent tools to record or manipulate respiratory rhythmogenic neurons. These resources will ultimately help elucidate the mechanisms that promote respiratory-related oscillations of preBötC Dbx1-derived neurons and thus breathing.
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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]. "
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    ABSTRACT: The transcription factor Pax6 is a crucial regulator of eye and central nervous system development. Both the spatiotemporal patterns and the precise levels of Pax6 expression are subject to tight control, mediated by an extensive set of cis-regulatory elements. Previous studies have shown that a YAC reporter transgene containing 420Kb of genomic DNA spanning the human PAX6 locus drives expression of a tau-tagged GFP reporter in mice in a pattern that closely resembles that of endogenous Pax6. Here we have closely compared the pattern of tau-GFP reporter expression at the cellular level in the forebrains and eyes of transgenic mice carrying either complete or truncated versions of the YAC reporter transgene with endogenous Pax6 expression and found several areas where expression of tau-GFP and Pax6 diverge. Some discrepancies are due to differences between the intracellular localization or perdurance of tau-GFP and Pax6 proteins, while others are likely to be a consequence of transcriptional differences. We show that cis-regulatory elements that lie outside the 420kb fragment of PAX6 are required for correct expression around the pallial-subpallial boundary, in the amygdala and the prethalamus. Further, we found that the YAC reporter transgene effectively labels cells that contribute to the lateral cortical stream, including cells that arise from the pallium and subpallium, and therefore represents a useful tool for studying lateral cortical stream migration.
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