Dopaminergic neurons modulate GABA neuron migration in the embryonic midbrain

Vasudevan, Anju; Won, Chung-Kil; Li, Suyan; Erdélyi, Ferenc; Szabó, Gábor; Kim, Kwang S.

doi:10.1242/dev.078394

Cited by 15 publications

(20 citation statements)

References 34 publications

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“…Thus, several potential migratory paths have been proposed for neurons that form the SN (see Introduction) (Hanaway et al, 1971;Kawano et al, 1995;Shults et al, 1990;Vasudevan et al, 2012). Our data show that DA neurons destined for the mVTA and SN undergo an initial radially oriented migration from the ventricular zone to the mantle layer.…”

Section: Discussion Migratory Paths Of Da Neuronsmentioning

confidence: 62%

“…DA neurons migrate from their ventral midline progenitor area to the mantle layer, where they settle in distinct clusters to form the SN, VTA or RRF. Two distinct migration models, based primarily on immunostaining for tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis and/or birthdating of ventral midbrain cells, have been put forward: (1) VTA and SN are primarily formed through radial migration (Hanaway et al, 1971), (2) DA neurons initially migrate radially towards the pial surface and then tangentially to form the VTA and SN (Kawano et al, 1995;Marchand and Poirier, 1983;Shults et al, 1990;Vasudevan et al, 2012). These studies could not unambiguously distinguish between different DA subpopulations during their migration phase nor did they monitor migratory behavior in real time.…”

Section: Introductionmentioning

confidence: 99%

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Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system

et al. 2014

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The proper functioning of the dopaminergic system requires the coordinated formation of projections extending from dopaminergic neurons in the substantia nigra (SN), ventral tegmental area (VTA) and retrorubral field to a wide array of forebrain targets including the striatum, nucleus accumbens and prefrontal cortex. The mechanisms controlling the assembly of these distinct dopaminergic cell clusters are not well understood. Here, we have investigated in detail the migratory behavior of dopaminergic neurons giving rise to either the SN or the medial VTA using genetic inducible fate mapping, ultramicroscopy, time-lapse imaging, slice culture and analysis of mouse mutants. We demonstrate that neurons destined for the SN migrate first radially and then tangentially, whereas neurons destined for the medial VTA undergo primarily radial migration. We show that tangentially migrating dopaminergic neurons express the components of the reelin signaling pathway, whereas dopaminergic neurons in their initial, radial migration phase express CXC chemokine receptor 4 (CXCR4), the receptor for the chemokine CXC motif ligand 12 (CXCL12). Perturbation of reelin signaling interferes with the speed and orientation of tangentially, but not radially, migrating dopaminergic neurons and results in severe defects in the formation of the SN. By contrast, CXCR4/CXCL12 signaling modulates the initial migration of dopaminergic neurons. With this study, we provide the first molecular and functional characterization of the distinct migratory pathways taken by dopaminergic neurons destined for SN and VTA, and uncover mechanisms that regulate different migratory behaviors of dopaminergic neurons.

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Section: Discussion Migratory Paths Of Da Neuronsmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system

et al. 2014

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“…However, this result was not surprising because, as mentioned above, we applied only three pulses of BrdU. Moreover, to minimize toxic effects, we used a smaller dose of BrdU compared to the 50 mg/kg dose that is routinely employed in many studies (Ogawa et al, 2012; Vasudevan et al, 2012). We also cannot exclude the possibility that BrdU incorporation affects the survival and proliferative activity of labeled cells (Kondo and Makita, 1997; Ross et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Our own pilot experiments with a single BrdU injection on each of these embryonic days confirmed the presence of these waves (unpublished observation). During this time of midbrain development, both dopaminergic and GABAergic neurons are born (Gates et al, 2006; Vasudevan et al, 2012; Achim et al, 2012). The BrdU administration regimen applied in our study, i.e., a low‐dose (30 mg/kg) injection given every 24 h on E12, E13 and E14, resulted in permanent BrdU incorporation into midbrain nuclei that was successfully observed even on PND 70.…”

Section: Discussionmentioning

confidence: 99%

Early‐life stress increases the survival of midbrain neurons during postnatal development and enhances reward‐related and anxiolytic‐like behaviors in a sex‐dependent fashion

Chocyk

Majcher-Maślanka

Przyborowska

et al. 2015

Intl J of Devlp Neuroscience

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Clinical studies have suggested that early-life stress (ELS) increases the risk of psychopathologies that are strongly associated with dysfunction of dopaminergic neurotransmission. Thus, ELS may interfere with the development and maturation of the dopaminergic system; however, the mechanisms involved in such interference are poorly understood. In the present study, we investigated the effect of ELS on the survival of specific populations of neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) during postnatal development. First, we injected bromodeoxyuridine (BrdU) into pregnant rat dams on embryonic days 12, 13 and 14 to permanently label midbrain neurons. Then, after birth, the dams and litters were subjected to a maternal separation (MS) procedure to model ELS conditions. The number of BrdU+ neurons and the total number of neurons (cresyl violet+, CV+) were estimated in both male and female juvenile, adolescent, and adult rats. Moreover, sucrose preference and anxiety-like behaviors were studied during adulthood. We found that MS permanently increased the number of BrdU+ and CV+ neurons in the VTA of males. In the SNc, a temporary increase in the number of BrdU+ neurons was observed in juvenile MS males; however, only adult MS males displayed an increase in the number of CV+ neurons. Immunofluorescence analysis implied that MS affected the fate of non-dopaminergic neurons. MS males displayed anxiolytic-like behavior and an increase in sucrose preference. These results suggest that ELS induces distinct dysregulation in the midbrain circuitry of males, which may lead to sex-specific psychopathology of the reward system.

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“…Once they have reached the basal part of the ventral midbrain, neurons that will ultimately constitute the SN migrate tangentially away from the midline resulting in the separation of SN and VTA (Figure 2.3B). 51,60,63–65 …”

Section: Mda and 5-ht Neurons Develop In Parallel And In Close Apposimentioning

confidence: 99%

Functional Interplay between Dopaminergic and Serotonergic Neuronal Systems during Development and Adulthood

Niederkofler

Asher

Dymecki

2015

ACS Chem. Neurosci.

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The complex integration of neurotransmitter signals in the nervous system contributes to the shaping of behavioral and emotional constitutions throughout development. Imbalance among these signals may result in pathological behaviors and psychiatric illnesses. Therefore, a better understanding of the interplay between neurotransmitter systems holds potential to facilitate therapeutic development. Of particular clinical interest are the dopaminergic and serotonergic systems, as both modulate a broad array of behaviors and emotions and have been implicated in a wide range of affective disorders. Here we review evidence speaking to an interaction between the dopaminergic and serotonergic neuronal systems across development. We highlight data stemming from developmental, functional, and clinical studies, reflecting the importance of this transmonoaminergic interplay.

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Dopaminergic neurons modulate GABA neuron migration in the embryonic midbrain

Cited by 15 publications

References 34 publications

Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system

Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system

Early‐life stress increases the survival of midbrain neurons during postnatal development and enhances reward‐related and anxiolytic‐like behaviors in a sex‐dependent fashion

Functional Interplay between Dopaminergic and Serotonergic Neuronal Systems during Development and Adulthood

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