Position and time specify the migration of a pioneering population of olfactory bulb interneurons

Department of Cell and Molecular Physiology, UNC Neuroscience Center, The University of North Carolina at Chapel Hill School of Medicine, NC 27599, USA.
Developmental Biology (Impact Factor: 3.55). 10/2006; 297(2):387-401. DOI: 10.1016/j.ydbio.2006.05.009
Source: PubMed


We defined the cellular mechanisms for genesis, migration, and differentiation of the initial population of olfactory bulb (OB) interneurons. This cohort of early generated cells, many of which become postmitotic on embryonic day (E) 14.5, differentiates into a wide range of mature OB interneurons by postnatal day (P) 21, and a substantial number remains in the OB at P60. Their precursors autonomously acquire a distinct identity defined by their position in the lateral ganglionic eminence (LGE). The progeny migrate selectively to the OB rudiment in a pathway that presages the rostral migratory stream. After arriving in the OB rudiment, these early generated cells acquire cellular and molecular hallmarks of OB interneurons. Other precursors--including those from the medial ganglionic eminence (MGE) and OB--fail to generate neuroblasts with similar migratory capacity when transplanted to the LGE. The positional identity and migratory specificity of the LGE precursors is rigidly established between E12.5 and E14.5. Thus, the pioneering population of OB interneurons is generated from spatially and temporally determined LGE precursors whose progeny uniquely recognize a distinct migratory trajectory.

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Available from: Franck Polleux, Feb 14, 2014
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    • "Local interneurons in the OB modulate the activity of mitral/tufted cells. OB interneurons begin to be produced as early as embryonic day (E) 12–14 (Stenman et al., 2003; Tucker et al., 2006). It has been shown that specific interneuron subtypes arise from molecularly defined progenitor pools in a spatially regulated manner (Stenman et al., 2003; Waclaw et al., 2006; Kohwi et al., 2007; Long et al., 2007; Merkle et al., 2007; Ventura and Goldman, 2007; Young et al., 2007; Xu et al., 2008). "
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    ABSTRACT: Interneurons in the olfactory bulb (OB) represent a heterogeneous population, which are first produced at embryonic stages and persisting into adulthood. Using the BrdU birthdating method combined with immunostaining for several different neuronal markers, we provide the integrated temporal patterns of distinct mouse OB interneuron production from embryonic day 14 to postnatal day 365. We show that although the majority of OB interneuron subtypes continue to be generated throughout life, most subtypes show a similar "bell-like" temporal production pattern with a peak around birth. Tyrosine hydroxylase and calretinin-expressing interneurons are produced at a relatively low rate in the adult OB, while parvalbumin-expressing (PV+) interneuron production is confined to later embryonic and early postnatal stages. We also show that Dlx5/6-expressing progenitors contribute to PV+ interneurons in the OB. Interestingly, all PV+ interneurons in the external plexiform layer (EPL) express the transcription factor Sp8. Genetic ablation of Sp8 by cre/loxP-based recombination severely reduces the number of PV+ interneurons in the EPL of the OB. Our results suggest that Sp8 is required for the normal production of PV+ interneurons in the EPL of the OB. These data expand our understanding of the temporal and molecular regulation of OB interneuron neurogenesis.
    The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 06/2011; 31(23):8450-5. DOI:10.1523/JNEUROSCI.0939-11.2011 · 6.34 Impact Factor
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    • "In the mouse, OB interneurons are first generated about embryonic day (E) 12–14 (Wichterle et al. 2001; Stenman et al. 2003; Tucker et al. 2006). However, the NSCs that produce these neurons in the embryo are morphologically very different from the NSCs that produce OB interneurons in the adult, likely due to the dramatic morphological changes that occur in the developing brain. "
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    ABSTRACT: Neural stem cells persist in the adult mammalian brain in a neurogenic niche known as the subventricular zone (SVZ). SVZ neural stem cells (NSCs) can self-renew and are multipotent in culture. In rodents, adult NSCs correspond to SVZ astrocytes (type B cells) that are derived from radial glia, the NSCs of the embryonic and early postnatal brain. Type B cells generate transit-amplifying (type C) cells that give rise to young neurons (type A cells) and oligodendrocytes. Young neurons are born throughout the adult neurogenic niche and migrate tangentially through a complex network of chains that merge into the rostral migratory stream (RMS), a major pathway that leads into the olfactory bulb (OB). Within the OB, young neurons differentiate into multiple types of interneurons. The SVZ was thought to be limited to the lateral wall of the lateral ventricle, but recent work shows that the adult neurogenic niche is significantly more extensive and includes portions of the medial and dorsal walls of the lateral ventricle and the RMS itself. Furthermore, several recent studies explain why young OB neurons are generated in such an extensive region. Type B cells in different regions of the SVZ, although able to self-renew and generate both neurons and glial cells in vitro, are heterogeneous and committed to producing defined neuronal subtypes in vivo. The adult SVZ therefore provides a rich system to study not only neural replacement, but also the cellular and molecular mechanisms underlying regionalization and cell-fate specification.
    Cold Spring Harbor Symposia on Quantitative Biology 12/2008; 73:357-65. DOI:10.1101/sqb.2008.73.019
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    • "In addition, these contacts are closely correlated with the entrance of the OSN axons at the initial ages (E14 and E15). Moreover, the significant increment in synapse number at E16 could be related to the presence of different cell types in the EPL (Ló pez- Mascaraque et al., 1990; Kosaka & Kosaka, 2005), and the contribution of OB cells originate from other telencephalic regions during development (Pencea & Luskin, 2003; Stenman et al., 2003; Tucker et al., 2006; Waclaw et al., 2006; Long et al., 2007; García- Moreno et al., 2008). These data lead us to think that these newly generated neurons, from other regions, could contribute to the establishment of the glomeruli and synaptogenesis in the OB. "
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    ABSTRACT: Synaptogenesis is essential for the development of neuronal networks in the brain. In the olfactory bulb (OB) glomeruli, numerous synapses must form between sensory olfactory neurons and the dendrites of mitral/tufted and periglomerular cells. Glomeruli develop from E13 to E16 in the mouse, coincident with an increment of the neuropil in the border between the external plexiform (EPL) and olfactory nerve layers (ONL), coupled to an extensive labelling of phalloidin and GAP-43 from the ONL to EPL. We have tracked synaptogenesis in the OB during this period by electron microscopy (EM) and immunolabelling of the transmembrane synaptic vesicle glycoprotein SV-2. No SV-2 labelling or synapses were detected at E13, although electrodense junctions lacking synaptic vesicles could be observed by EM. At E14, sparse SV-2 labelling appears in the most ventral and medial part of the incipient OB, which displays a ventro-dorsal gradient by E15 but covers the entire OB by E16. These data establish a spatio-temporal pattern of synaptogenesis, which perfectly matches with the glomeruli formation in developing OB.
    European Journal of Neuroscience 07/2008; 27(11):2838-46. DOI:10.1111/j.1460-9568.2008.06283.x · 3.18 Impact Factor
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