Ikaros‐1 couples cell cycle arrest of late striatal precursors with neurogenesis of enkephalinergic neurons

Martín‐Ibáñez, Raquel; Crespo, Empar; Urbán, Noelia; Sergent‐Tanguy, Solène; Herranz, Cristina; Jaumot, Montserrat; Valiente, Manuel; Long, Jason E.; Pineda, José Ramón; Andreu, Celia; Rubenstein, John L.R.; Marı́n, Oscar; Georgopoulos, Katia; Mengod, Guadalupe; Fariñas, Isabel; Bachs, Oriol; Alberch, Jordi; Canals, Josep M.

doi:10.1002/cne.22215

Cited by 37 publications

(17 citation statements)

References 93 publications

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“…Besides the apparent similar function between He and Ikaros on ENK + neurogenesis, there is much evidence that they determine different ENK + subpopulations. They are expressed by different cells (Martín-Ibáñez et al, 2012), and their expression is not modified in the reciprocal knockout mice (Martín-Ibáñez et al, 2010, 2012). These results are contrary to the role of Ikaros family members in the hematopoietic system where they directly interact (Hahm et al, 1998; John et al, 2009), suggesting specific mechanisms of action in each system.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the transcription factors Ebf1, Isl1, Ctip2 (also known as Bcl11b), and Ikaros family members are mainly expressed in the MZ of the LGE where they regulate terminal differentiation of striatal projection neurons (Arlotta et al, 2008; Ehrman et al, 2013; Garcia-Dominguez et al, 2003; Garel et al, 1999; Lobo et al, 2006, 2008; Martín-Ibáñez et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

“…Ikaros is the founder member of this family of DNA-binding proteins, which consists of Ikaros, Helios (He), Aiolos, Eos and Pegasus (Ikzf1-5, respectively – Mouse Genome Informatics) (John et al, 2009; Rebollo and Schmitt, 2003; Yoshida and Georgopoulos, 2014). In addition, Ikaros has been implicated in CNS development (Agoston et al, 2007; Alsiö et al, 2013; Martín-Ibáñez et al, 2010). We have recently described that He is also implicated in striatal development (Martín-Ibáñez et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

et al. 2017

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Here, we unravel the mechanism of action of the Ikaros family zinc finger protein Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons, which express dopamine 2 receptor and enkephalin. To exert this effect, He is expressed in neural progenitor cells (NPCs) keeping them in the G1/G0 phase of the cell cycle. Thus, a lack of He results in an increase of S-phase entry and S-phase length of NPCs, which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ), which end up dying at postnatal stages. Therefore, He−/− mice show a reduction in the number of dorso-medial striatal MSNs in the adult that produces deficits in motor skills acquisition. In addition, overexpression of He in NPCs induces misexpression of DARPP-32 when transplanted in mouse striatum. These findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

et al. 2017

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“…A number of developmental control genes have been shown to play a role in the specification and/or differentiation of SPNs including the Gsx2, Ascl1 and Dlx transcription factors (Anderson et al, 1997; Toresson and Campbell, 2001; Yun et al, 2002, 2003; Waclaw et al, 2004; Long et al, 2009; Wang et al, 2009, 2011, 2013). The zinc finger transcription factors Ikaros and Helios as well as the early B-cell factor (Ebf1) have been shown to play crucial roles in the differentiation of the late born SPNs belonging to the matrix compartment (Garel et al, 1999; Martin-Ibanez et al, 2010, 2012). Studies in recent years have begun to shed light on the molecular genetic mechanisms that control the development of the direct and indirect SPN pathways.…”

Section: Introductionmentioning

confidence: 99%

“…Studies in recent years have begun to shed light on the molecular genetic mechanisms that control the development of the direct and indirect SPN pathways. In this respect, Ikaros and Sp9 are required for the normal differentiation and survival of the indirect SPNs (Martin-Ibanez et al, 2010; Zhang et al, 2016). Conversely, Ebf1 (Garel et al, 1999; Lobo et al, 2006, 2008) and the LIM homeodomain protein, Isl1 (Ehrman et al, 2013; Lu et al, 2014) have been implicated in the development of the direct pathway (i.e.…”

Section: Introductionmentioning

confidence: 99%

Foxo1 is a downstream effector of Isl1 in direct pathway striatal projection neuron development within the embryonic mouse telencephalon

Waclaw

Ehrman

Merchan-Sala

et al. 2017

Molecular and Cellular Neuroscience

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Recent studies have shown that the LIM-homeodomain transcription factor Isl1 is required for the survival and differentiation of direct pathway striatonigral neurons during embryonic development. The downstream effectors of Isl1 in these processes are presently unknown. We show here that Foxo1, a transcription factor that has been implicated in cell survival, is expressed in striatal projection neurons (SPNs) that derive from the Isl1 lineage (i.e. direct pathway SPNs). Moreover, Isl1 conditional knockouts (cKOs) show a severe loss of Foxo1 expression at E15.5 with a modest recovery by E18.5. Although Foxo1 is enriched in the direct pathway SPNs at embryonic stages, it is expressed in both direct and indirect pathway SPNs at postnatal time points as evidenced by co-localization with EGFP in both Drd1-EGFP and Drd2-EGFP BAC transgenic mice. Foxo1 was not detected in striatal interneurons as marked by the transcription factor Nkx2.1. Conditional knockout of Foxo1 using Dlx5/6-CIE results in reduced expression of the SPN marker Darpp-32, as well as in the direct pathway SPN markers Ebf1 and Zfp521 within the embryonic striatum at E15.5. However, this phenotype improves in the conditional mutants by E18.5. Interestingly, the Foxo family members, Foxo3 and Foxo6, remain expressed at late embryonic stages in the Foxo1 cKOs unlike the Isl1 cKOs where Foxo1/3/6 as well as the Foxo1/3 target Bach2 are all reduced. Taken together, these findings suggest that Foxo-regulated pathways are downstream of Isl1 in the survival and/or differentiation of direct pathway SPNs.

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Evolution of the basal ganglia: Dual‐output pathways conserved throughout vertebrate phylogeny

Stephenson-Jones

Ericsson

Robertson

et al. 2012

J of Comparative Neurology

111

104

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The basal ganglia, including the striatum, globus pallidus interna and externa (GPe), subthalamic nucleus (STN), and substantia nigra pars compacta, are conserved throughout vertebrate phylogeny and have been suggested to form a common vertebrate mechanism for action selection. In mammals, this circuitry is further elaborated by the presence of a dual-output nucleus, the substantia nigra pars reticulata (SNr), and the presence of modulatory input from the cholinergic pedunculopontine nucleus (PPN). We sought to determine whether these additional components of the mammalian basal ganglia are also present in one of the phylogenetically oldest vertebrates, the lamprey. We show, by using immunohistochemistry, tract tracing, and whole-cell recordings, that homologs of the SNr and PPN are present in the lamprey. Thus the SNr receives direct projections from inwardly rectifying γ-aminobutyric acid (GABA)-ergic striatal neurons expressing substance P, but it is also influenced by indirect basal ganglia projections from the STN and potentially the GPe. Moreover, GABAergic SNr projection neurons are tonically active and project to the thalamus and brainstem motor areas. The homolog of the PPN contains both cholinergic and GABAergic neurons and is connected with all the nuclei of the basal ganglia, supporting its proposed role as part of an extended basal ganglia. A separate group of cholinergic neurons dorsal to the PPN corresponds to the descending mesencephalic locomotor region. Our results suggest that dual-output nuclei are part of the ancestral basal ganglia and that the PPN appears to have coevolved as part of a mechanism for action selection common to all vertebrates.

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Ikaros‐1 couples cell cycle arrest of late striatal precursors with neurogenesis of enkephalinergic neurons

Cited by 37 publications

References 93 publications

Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

Foxo1 is a downstream effector of Isl1 in direct pathway striatal projection neuron development within the embryonic mouse telencephalon

Evolution of the basal ganglia: Dual‐output pathways conserved throughout vertebrate phylogeny

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