Loss of COUP-TFI Alters the Balance between Caudal Ganglionic Eminence- and Medial Ganglionic Eminence-Derived Cortical Interneurons and Results in Resistance to Epilepsy

Lodato, Simona; Tomassy, Giulio Srubek; Leonibus, Elvira De; Uzcategui, Yoryani G.; Andolfi, Gennaro; Armentano, Maria Francesca; Touzot, Audrey; Gaztelu, J.M.; Arlotta, Paola; Prida, Liset Menéndez de la; Studer, Michèle

doi:10.1523/jneurosci.6580-10.2011

Cited by 100 publications

(110 citation statements)

References 56 publications

(103 reference statements)

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“…Previous work on Coup-TF1 and Coup-TF2 in the embryonic basal ganglia focused on their function in the caudal ganglionic eminence (CGE) and amygdala (Lodato et al, 2011;Tang et al, 2012), although loss of Coup-TF1 decreased SST/PV balance (Lodato et al, 2011). Here, through conditional mutagenesis, forced expression and transplantation we demonstrate that Coup-TF2, in conjunction with Coup-TF1, regulate cell cycle dynamics and cell fate decisions, including apoptosis, in MGE progenitors, but not in neurons.…”

Section: Introductionmentioning

confidence: 72%

“…We focused on Coup-TF2 (Nr2f2) function (steroid/thyroid hormone receptor superfamily member) because it, and its paralogue Coup-TF1 (Nr2f1), are expressed in the MGE, and are largely confined to layer V SST + CINs (Cai et al, 2013;Lodato et al, 2011). Previous work on Coup-TF1 and Coup-TF2 in the embryonic basal ganglia focused on their function in the caudal ganglionic eminence (CGE) and amygdala (Lodato et al, 2011;Tang et al, 2012), although loss of Coup-TF1 decreased SST/PV balance (Lodato et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived neocortical interneurons

Vogt

Lindtner

et al. 2017

Development

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Distinct cortical interneuron (CIN) subtypes have unique circuit functions; dysfunction in specific subtypes is implicated in neuropsychiatric disorders. Somatostatin-and parvalbuminexpressing (SST + and PV + ) interneurons are the two major subtypes generated by medial ganglionic eminence (MGE) progenitors. Spatial and temporal mechanisms governing their cellfate specification and differential integration into cortical layers are largely unknown. We provide evidence that Coup-TF1 and Coup-TF2 (Nr2f1 and Nr2f2) transcription factor expression in an arc-shaped progenitor domain within the MGE promotes time-dependent survival of this neuroepithelium and the time-dependent specification of layer V SST + CINs. Coup-TF1 and Coup-TF2 autonomously repress PV + fate in MGE progenitors, in part through directly driving Sox6 expression. These results have identified, in mouse, a transcriptional pathway that controls SST-PV fate.

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Section: Introductionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived neocortical interneurons

Vogt

Lindtner

et al. 2017

Development

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“…Here, we address this issue focusing on the OB, a highly plastic region of the adult mammalian brain, characterised by continuous neurogenesis (Lledo et al, 2008). We show that in the adult OB, as in the cerebral cortex (Lodato et al, 2011), COUP-TFI is expressed in distinct subpopulations of GABAergic interneurons. Little or no staining was observed in migrating neuroblasts, indicating that COUP-TFI expression in the OB is mostly associated with mature cells integrated in the GcL and GL.…”

Section: Discussionmentioning

confidence: 98%

“…COUP-TFI, a member of the orphan nuclear receptor family, plays multiple roles in neuronal development (Park et al, 2003;Alfano et al, 2013). It is highly expressed in the developing telencephalon (Qiu et al, 1994;Armentano et al, 2006), where it regulates the balance of cortical patterning between frontal/motor and sensory areas (Armentano et al, 2007), and is involved in the migration and specification of cortical GABAergic interneurons in the subpallium (Tripodi et al, 2004;Lodato et al, 2011). Here, we show that COUP-TFI is co-expressed with TH in the vast majority of DAergic neurons in the OB, in an activity-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

COUP-TFI controls activity-dependent tyrosine hydroxylase expression in adult dopaminergic olfactory bulb interneurons

et al. 2013

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COUP-TFI is an orphan nuclear receptor acting as a strong transcriptional regulator in different aspects of forebrain embryonic development. In this study, we investigated COUP-TFI expression and function in the mouse olfactory bulb (OB), a highly plastic telencephalic region in which continuous integration of newly generated inhibitory interneurons occurs throughout life. OB interneurons belong to different populations that originate from distinct progenitor lineages. Here, we show that COUP-TFI is highly expressed in tyrosine hydroxylase (TH)-positive dopaminergic interneurons in the adult OB glomerular layer (GL). We found that odour deprivation, which is known to downregulate TH expression in the OB, also downregulates COUP-TFI in dopaminergic cells, indicating a possible correlation between TH-and COUP-TFI-activitydependent action. Moreover, we demonstrate that conditional inactivation of COUP-TFI in the EMX1 lineage results in a significant reduction of both TH and ZIF268 expression in the GL. Finally, lentiviral vector-mediated COUP-TFI deletion in adult-generated interneurons confirmed that COUP-TFI acts cell-autonomously in the control of TH and ZIF268 expression. These data indicate that COUP-TFI regulates TH expression in OB cells through an activitydependent mechanism involving ZIF268 induction and strongly argue for a maintenance rather than establishment function of COUP-TFI in dopaminergic commitment. Our study reveals a previously unknown role for COUP-TFI in the adult brain as a key regulator in the control of sensory-dependent plasticity in olfactory dopaminergic neurons.

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“…Of note, it has also been reported that removal of Shh from the MGE mantle reduces both SST and PV interneurons by similar proportions (Flandin et al, 2011). However, as PV interneurons might preferentially originate from MGE subventricular zone (SVZ) divisions that would be closer to the MGE mantle source of Shh (Glickstein et al, 2007;Lodato et al, 2011), the net effect of Shh loss in the MGE mantle on cIN composition is difficult to determine without knowing how Shh signaling itself is altered by this loss within the various populations of MGE progenitors.…”

Section: Discussionmentioning

confidence: 99%

Duration of culture and sonic hedgehog signaling differentially specify PV versus SST cortical interneuron fates from embryonic stem cells

et al. 2015

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Medial ganglionic eminence (MGE)-derived GABAergic cortical interneurons (cINs) consist of multiple subtypes that are involved in many cortical functions. They also have a remarkable capacity to migrate, survive and integrate into cortical circuitry after transplantation into postnatal cortex. These features have engendered considerable interest in generating distinct subgroups of interneurons from pluripotent stem cells (PSCs) for the study of interneuron fate and function, and for the development of cell-based therapies. Although advances have been made, the capacity to generate highly enriched pools of subgroup fatecommitted interneuron progenitors from PSCs has remained elusive. Previous studies have suggested that the two main MGE-derived interneuron subgroups -those expressing somatostatin (SST) and those expressing parvalbumin (PV) -are specified in the MGE from Nkx2.1-expressing progenitors at higher or lower levels of sonic hedgehog (Shh) signaling, respectively. To further explore the role of Shh and other factors in cIN fate determination, we generated a reporter line such that Nkx2.1-expressing progenitors express mCherry and postmitotic Lhx6-expressing MGE-derived interneurons express GFP. Manipulations of Shh exposure and time in culture influenced the subgroup fates of ESC-derived interneurons. Exposure to higher Shh levels, and collecting GFP-expressing precursors at 12 days in culture, resulted in the strongest enrichment for SST interneurons over those expressing PV, whereas the strongest enrichment for PV interneurons was produced by lower Shh and by collecting mCherry-expressing cells after 17 days in culture. These findings confirm that fate determination of cIN subgroups is crucially influenced by Shh signaling, and provide a system for the further study of interneuron fate and function.

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Loss of COUP-TFI Alters the Balance between Caudal Ganglionic Eminence- and Medial Ganglionic Eminence-Derived Cortical Interneurons and Results in Resistance to Epilepsy

Cited by 100 publications

References 56 publications

Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived neocortical interneurons

Coup-TF1 and Coup-TF2 control subtype and laminar identity of MGE-derived neocortical interneurons

COUP-TFI controls activity-dependent tyrosine hydroxylase expression in adult dopaminergic olfactory bulb interneurons

Duration of culture and sonic hedgehog signaling differentially specify PV versus SST cortical interneuron fates from embryonic stem cells

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