Molecules and Mechanisms Involved in the Generation and Migration of Cortical Interneurons

Hernández-Miranda, Luis R.; Parnavelas, John G.; Chiara, Francesca

doi:10.1042/an20090053

Cited by 78 publications

(97 citation statements)

References 154 publications

(227 reference statements)

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“…Many signalling molecules participate in the modulation of neuronal migration, including molecules classified as neurotransmitters and as growth/differentiation factors [2,3]. …”

Section: Introductionmentioning

confidence: 99%

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

et al. 2011

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BackgroundA number of studies have separately shown that the neuregulin1 (NRG1)/ErbB4 system and NMDA-type glutamate receptors (NMDARs) are involved in several aspects of neuronal migration. In addition, intracellular calcium fluctuations play central roles in neuronal motility. Stable expression of the tyrosine kinase receptor ErbB4 promotes migratory activity in the neural progenitor cell line ST14A upon NRG1 stimulation. In this work we analyzed the potential interactions between the NRG1/ErbB4 system and NMDARs in the ST14A migratory process as well as its calcium dependence.ResultsRT-PCR studies have shown that both native ST14A cells (non-expressing ErbB4), as well as ErbB4-transfected cells express low levels of a restricted number of NMDAR subunits: NR1, NR2C, NR2D and NR3B. The resulting NMDAR would form Ca2+ channels characterized by low Mg2+-sensitivity and low Ca2+-permeability, generating small, long-lasting currents. Ca2+-imaging experiments showed slow [Ca2+]i increases in 45% of the cells following 8 μM NMDA stimulation. Basal migration of ErbB4-transfected ST14A cells was unaffected by 18 hrs NMDA incubation. However, over the same incubation time, NMDA was able to significantly enhance NRG1-induced migration. Pre-incubation with the intracellular calcium chelator BAPTA-AM reduced both NRG1- and NRG1/NMDA-stimulated migration, suggesting the involvement of Ca2+ in these processes. NRG1 stimulation of ErbB4-transfected ST14A cells induced a sustained, long-lasting increase in [Ca2+]i, in 99% of the cells. These intracellular Ca2+ signals could be ascribed to both release from intracellular stores and influx from the extracellular medium trough a mechanism of store-operated calcium entry (SOCE). Short-time co-incubation of NMDA and NRG1 did not substantially modify the NRG1-induced intracellular calcium signals.ConclusionsIn summary, NRG1 stimulation of the ErbB4 receptor exerts a sustained [Ca2+]i increase in ST14A neural progenitors; NRG1-induced migration is Ca2+-dependent and can be positively modulated by activation of the NMDA receptor.

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“…Many signalling molecules participate in the modulation of neuronal migration, including molecules classified as neurotransmitters and as growth/differentiation factors [2,3]. …”

Section: Introductionmentioning

confidence: 99%

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

et al. 2011

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“…Recently, we and others identified two different corridors for tangentially migrating cortical interneurons in the basal telencephalon: the DMS originating from the MGE and the SMS originating mainly from the POA (Gelman et al, 2009;Hernández-Miranda et al, 2010;Zimmer et al, 2011). Because our in situ hybridization and immunohistochemical data demonstrate that EphA4 is predominantly expressed along the DMS, but not on the SMS, we also tested whether the effect of EphA4-Fc on interneurons is cell type specific.…”

Section: Epha4 Is a Motogenic Factor For Cortical Interneuronsmentioning

confidence: 99%

“…Previous studies have already proposed different soluble molecules as motogenic factors for cortical interneurons (reviewed by Hernández-Miranda et al, 2010). For example, it has been suggested that members of the neurotrophin family, BDNF and neurotrophin 4 (NT4; now known as neurotrophin 5, Ntf5), stimulate interneuron migration in vitro (Polleux et al, 2002).…”

Section: Molecular Motors and Breaks For Migrating Interneuronsmentioning

confidence: 99%

EphA/ephrin A reverse signaling promotes the migration of cortical interneurons from the medial ganglionic eminence

et al. 2014

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Inhibitory interneurons control the flow of information and synchronization in the cerebral cortex at the circuit level. During embryonic development, multiple subtypes of cortical interneurons are generated in different regions of the ventral telencephalon, such as the medial and caudal ganglionic eminence (MGE and CGE), as well as the preoptic area (POA). These neurons then migrate over long distances towards their cortical target areas. Diverse families of diffusible and cell-bound signaling molecules, including the Eph/ephrin system, regulate and orchestrate interneuron migration. Ephrin A3 and A5, for instance, are expressed at the borders of the pathway of MGE-derived interneurons and prevent these cells from entering inappropriate regions via EphA4 forward signaling. We found that MGE-derived interneurons, in addition to EphA4, also express ephrin A and B ligands, suggesting Eph/ephrin forward and reverse signaling in the same cell. In vitro and in vivo approaches showed that EphA4-induced reverse signaling in MGE-derived interneurons promotes their migration and that this effect is mediated by ephrin A2 ligands. In EphA4 mutant mice, as well as after ephrin A2 knockdown using in utero electroporation, we found delayed interneuron migration at embryonic stages. Thus, besides functions in guiding MGE-derived interneurons to the cortex through forward signaling, here we describe a novel role of the ephrins in driving these neurons to their target via reverse signaling.

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“…En route to the cortex, migrating MGE‐derived interneurons encounter the developing striatum and avoid it (Marin and Rubenstein, 2003; Métin et al, 2006). Work over the last decade has identified some of the cellular and molecular mechanisms that guide their migration through the ventral telencephalon (for review see Hernandez‐Miranda et al, 2010; Faux et al, 2012). These include class 3 semaphorin ligands and their receptors, the neuropilins (Nrps) and plexins.…”

mentioning

confidence: 99%

Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice

Andrews

Davidson

Tamamaki

et al. 2015

J of Comparative Neurology

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Cortical interneurons are generated predominantly in the medial ganglionic eminence (MGE) and migrate through the ventral and dorsal telencephalon before taking their final positions within the developing cortical plate. Previously we demonstrated that interneurons from Robo1 knockout (Robo1−/−) mice contain reduced levels of neuropilin 1 (Nrp1) and PlexinA1 receptors, rendering them less responsive to the chemorepulsive actions of semaphorin ligands expressed in the striatum and affecting their course of migration (Hernandez‐Miranda et al. [2011] J. Neurosci. 31:6174–6187). Earlier studies have highlighted the importance of Nrp1 and Nrp2 in interneuron migration, and here we assess the role of PlexinA1 in this process. We observed significantly fewer cells expressing the interneuron markers Gad67 and Lhx6 in the cortex of PlexinA1 −/− mice compared with wild‐type littermates at E14.5 and E18.5. Although the level of apoptosis was similar in the mutant and control forebrain, proliferation was significantly reduced in the former. Furthermore, progenitor cells in the MGE of PlexinA1 −/− mice appeared to be poorly anchored to the ventricular surface and showed reduced adhesive properties, which may account for the observed reduction in proliferation. Together our data uncover a novel role for PlexinA1 in forebrain development. J. Comp. Neurol. 524:518–534, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

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Molecules and Mechanisms Involved in the Generation and Migration of Cortical Interneurons

Cited by 78 publications

References 154 publications

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

Neuregulin1/ErbB4-induced migration in ST14A striatal progenitors: calcium-dependent mechanisms and modulation by NMDA receptor activation

EphA/ephrin A reverse signaling promotes the migration of cortical interneurons from the medial ganglionic eminence

Altered proliferative ability of neuronal progenitors in PlexinA1 mutant mice

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