Reelin sets the pace of neocortical neurogenesis

Lakomá, Jarmila; García‐Alonso, Luis; Luque, Juan M.

doi:10.1242/dev.063776

Cited by 53 publications

(33 citation statements)

References 52 publications

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“…Further examination of the cortical structure under higher magnification revealed that the Bloc1s2 −/− cortical plate (CP) and intermediate zone (IZ) were remarkably thinner than WT, while the thickness of the ventricular zone (VZ) was comparable between WT and mutant (Figure 1G and H). Due to the significant reduction in cortical wall thickness, we next investigated the effect of loss of BLOS2 on early cortical neurogenesis by immunostaining with the deep-layer-specific markers Ctip2 (layer V and VI) and Tbr1 (layer VI) (Lakomá et al, 2011). At E12.5 and E14.5, Ctip2 + early-born layer V and VI neurons and Tbr1 + layer VI neurons were all significantly reduced in number in the Bloc1s2 −/− cortex compared to the control (Figure 1I to Figure 1K), suggesting that BLOS2 ablation impairs early cortical neurogenesis.…”

Section: Resultsmentioning

confidence: 99%

BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development

Zhou

Zhang

et al. 2016

eLife

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Notch signaling plays a crucial role in controling the proliferation and differentiation of stem and progenitor cells during embryogenesis or organogenesis, but its regulation is incompletely understood. BLOS2, encoded by the Bloc1s2 gene, is a shared subunit of two lysosomal trafficking complexes, biogenesis of lysosome-related organelles complex-1 (BLOC-1) and BLOC-1-related complex (BORC). Bloc1s2−/− mice were embryonic lethal and exhibited defects in cortical development and hematopoiesis. Loss of BLOS2 resulted in elevated Notch signaling, which consequently increased the proliferation of neural progenitor cells and inhibited neuronal differentiation in cortices. Likewise, ablation of bloc1s2 in zebrafish or mice led to increased hematopoietic stem and progenitor cell production in the aorta-gonad-mesonephros region. BLOS2 physically interacted with Notch1 in endo-lysosomal trafficking of Notch1. Our findings suggest that BLOS2 is a novel negative player in regulating Notch signaling through lysosomal trafficking to control multiple stem and progenitor cell homeostasis in vertebrates.DOI: http://dx.doi.org/10.7554/eLife.18108.001

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Section: Resultsmentioning

confidence: 99%

BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development

Zhou

Zhang

et al. 2016

eLife

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“…Prominent among the myriad intrinsic and extrinsic factors that contribute to establishing proper cortical form and function are the reelin-secreting Cajal–Retzius cells. They orchestrate cortico-genetic events such as proliferation, migration, and positioning of immature cortical neurons, the interplay of which culminate in the well-documented developmental role of Cajal–Retzius cells and reelin in staging the tightly coordinated inside-out patterning and layering of the cortex (D'Arcangelo et al, 1995; Franco et al, 2011; Frotscher, 1998; Gil-Sanz et al, 2013; Gupta et al, 2003; Hirotsune et al, 1995; Jossin and Cooper, 2011; Lakom a et al, 2011; Ogawa et al, 1995; Olson et al, 2006; Sekine et al, 2011; Supèr et al, 2000). …”

Section: Discussionmentioning

confidence: 99%

“…Cajal–Retzius cells, as the transient and first-born neurons of the embryonic rodent cortex, arise from pallial and subpallial origins and migrate tangentially below the pial surface to cover the entire neocortex (Bielle et al, 2005; García-Moreno et al, 2007). They release the glycoprotein reelin (D'Arcangelo et al, 1995; Hirotsune et al, 1995; Ogawa et al, 1995), implicated in regulating neuronal migration, layering, and neurogenesis in the developing cortex (Franco et al, 2011; Frotscher, 1998; Gil-Sanz et al, 2013; Gupta et al, 2003; Jossin and Cooper, 2011; Lakomá et al, 2011; Olson et al, 2006; Sekine et al, 2011). Thus, Cajal–Retzius cells are in a favorable position to orchestrate early aspects of corticogenesis, cortical patterning, and the establishment of nascent cortical circuits (Schwartz et al, 1998; Soriano and Del Río, 2005).…”

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confidence: 99%

Effects of Ethanol Exposure In Utero on Cajal–Retzius Cells in the Developing Cortex

Skorput

Yeh

2015

Alcoholism Clin & Exp Res

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Background Prenatal exposure to ethanol exerts teratogenic effects on the developing brain. Here, we tested the hypothesis that exposure to ethanol in utero alters the disposition of Cajal–Retzius cells that play a key role in orchestrating proliferation, migration, and laminar integration of cortical neurons in the embryonic cortex. Methods Pregnant Ebf2-EGFP mice, harboring EGFP-fluorescent Cajal–Retzius cells, were subjected to a 2% w/w ethanol consumption regimen starting at neural tube closure and lasting throughout gestation. Genesis of Cajal–Retzius cells was assessed by means of 5-bromo-2-deoxyuridine (BrdU) immunofluorescence at embryonic day 12.5, their counts and distribution were determined between postnatal day (P)0 and P4, patch clamp electrophysiology was performed between P2 and P3 to analyze GABA-mediated synaptic activity, and open-field behavioral testing was conducted in P45-P50 adolescents. Results In Ebf2-EGFP embryos exposed to ethanol in utero, we found increased BrdU labeling and expanded distribution of Cajal–Retzius cells in the cortical hem, pointing to increased genesis and proliferation. Postnatally, we found an increase in Cajal–Retzius cell number in cortical layer I. In addition, they displayed altered patterning of spontaneous GABA-mediated synaptic barrages and enhanced GABA-mediated synaptic activity, suggesting enhanced GABAergic tone. Conclusions These findings, together, underscore that Cajal–Retzius cells contribute to the ethanol-induced aberration of cortical development and abnormal GABAergic neurotransmission at the impactful time when intracortical circuits form.

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“…Timed pregnant EGFP mice were used to prepare cortical NSC cultures as previously described with some modifications (Mi et al 2005; Lakoma et al 2011). Briefly, E14–E15 mouse cortices were dissected and mechanically dissociated.…”

Section: Methodsmentioning

confidence: 99%

Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo

Chen

Yang

et al. 2016

Cereb. Cortex

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Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca2+ imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca2+ signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo.

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Reelin sets the pace of neocortical neurogenesis

Cited by 53 publications

References 52 publications

BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development

BLOS2 negatively regulates Notch signaling during neural and hematopoietic stem and progenitor cell development

Effects of Ethanol Exposure In Utero on Cajal–Retzius Cells in the Developing Cortex

Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo

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