Compromised generation of GABAergic interneurons in the brains of<i>Vax1</i>-/- mice

Taglialatela, Paola; Soria, José Miguel; Caironi, Veronica; Moiana, Alessia; Bertuzzi, Stefano

doi:10.1242/dev.01299

Cited by 52 publications

(49 citation statements)

References 66 publications

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“…The expression of Mash1 (bHLH) and Vax1 (homeobox) in Arx mutants appeared normal at E12.5; these genes are required for multiple steps in subpallial development (Casarosa et al, 1999;Yun et al, 2002;Taglialatela et al, 2004) (Fig. 4 A, B) (data not shown).…”

Section: Analysis Of Prenatal Subcortical Patterning and Differentiationmentioning

confidence: 92%

Inactivation ofArx, the Murine Ortholog of the X-Linked Lissencephaly with Ambiguous Genitalia Gene, Leads to Severe Disorganization of the Ventral Telencephalon with Impaired Neuronal Migration and Differentiation

Colombo¹,

Collombat²,

Colasante³

et al. 2007

J. Neurosci.

128

134

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ARX loss-of-function mutations cause X-linked lissencephaly with ambiguous genitalia (XLAG), a severe neurological condition that results in profound brain malformations, including microcephaly, absence of corpus callosum, and impairment of the basal ganglia. Despite such dramatic defects, their nature and origin remain largely unknown. Here, we used Arx mutant mice as a model to characterize the cellular and molecular mechanisms underlying the basal ganglia alterations. In these animals, the early differentiation of this tissue appeared normal, whereas subsequent differentiation was impaired, leading to the periventricular accumulation of immature neurons in both the lateral ganglionic eminence and medial ganglionic eminence (MGE). Both tangential migration toward the cortex and striatum and radial migration to the globus pallidus and striatum were greatly reduced in the mutants, causing a periventricular accumulation of NPYϩ or calretininϩ neurons in the MGE. Arx mutant neurons retained their differentiation potential in vitro but exhibited deficits in morphology and migration ability. These findings imply that cell-autonomous defects in migration underlie the neuronal localization defects. Furthermore, Arx mutants lacked a large fraction of cholinergic neurons and displayed a strong impairment of thalamocortical projections, in which major axon fiber tracts failed to traverse the basal ganglia. Altogether, these results highlight the critical functions of Arx in promoting neural migration and regulating basal ganglia differentiation in mice, consistent with the phenotype of XLAG patients.

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Section: Analysis Of Prenatal Subcortical Patterning and Differentiationmentioning

confidence: 92%

Inactivation ofArx, the Murine Ortholog of the X-Linked Lissencephaly with Ambiguous Genitalia Gene, Leads to Severe Disorganization of the Ventral Telencephalon with Impaired Neuronal Migration and Differentiation

Colombo¹,

Collombat²,

Colasante³

et al. 2007

J. Neurosci.

128

134

View full text Add to dashboard Cite

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“…Embryos were obtained from pregnant females at various stages of development. Noon of the day when the vaginal plug was identified was considered as E0.5, and embryos were subsequently staged according to morphological criteria and processed as described previously (Taglialatela et al, 2004).…”

Section: Vax1mentioning

confidence: 99%

“…In situ hybridization was performed on frozen sections with digoxigeninlabeled probes, as described previously (Taglialatela et al, 2004). Reactive tissues were revealed by incubation with the alkaline phosphatase substrate BM-Purple (Roche).…”

Section: In Situ Rna Hybridizationmentioning

confidence: 99%

“…Experiments were performed as described previously (Taglialatela et al, 2004). To trace the migratory pathway of neurons from the lateral ganglionic eminence (LGE) to the OB, we placed small crystals of 1,1Ј-dyoctodecyl-3,3,3Ј,3Ј-tetramethylindocarbocyanine (DiI) (Molecular Probes, Eugene, OR), or a piece of bamboo soaked in DiI, in the region of interest.…”

Section: Organotypic Slice Culturesmentioning

confidence: 99%

“…Experiments were performed as described previously (Taglialatela et al, 2004). Pregnant mothers and early postnatal mice were given intraperi-toneal injections of a dose of 100 mg of BrdU/gm of body weight.…”

Section: In Vivo Birthdating Analysismentioning

confidence: 99%

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Defective Postnatal Neurogenesis and Disorganization of the Rostral Migratory Stream in Absence of theVax1Homeobox Gene

Soria¹,

Taglialatela²,

Gil-Perotín³

et al. 2004

J. Neurosci.

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The subventricular zone (SVZ) is one of the sources of adult neural stem cells (ANSCs) in the mouse brain. Precursor cells proliferate in the SVZ and migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate into granule and periglomerular cells. Few transcription factors are known to be responsible for regulating NSC proliferation, migration, and differentiation processes; even fewer have been found to be responsible for the organization of the SVZ and RMS. For this reason, we studied the ventral anterior homeobox (Vax1) gene in NSC proliferation and in SVZ organization. We found that Vax1 is strongly expressed in the SVZ and in the RMS and that, in the absence of Vax1, embryonic precursor cells proliferate 100 times more than wild-type controls, in vitro. The SVZ of Vax1 Ϫ/Ϫ brains is hyperplastic and mostly disorganized, and the RMS is missing, causing a failure of precursor cell migration to the OBs, which as a result are severely hypoplastic. Moreover, we found that Vax1 is essential for the correct differentiation of ependyma and astrocytes.Together, these data indicate that Vax1 is a potent regulator of SVZ organization and NSC proliferation, with important consequences on postnatal neurogenesis.

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Radial glia in the ventral telencephalon

García

Harwell

2017

FEBS Letters

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The ventral telencephalon is the developmental origin of the basal ganglia and the source of neuronal and glial cells that integrate into developing circuits in other areas of the brain. Radial glia in the embryonic subpallium give rise to an enormous diversity of mature cell types, either directly or through other transit-amplifying progenitors. Here, we review current knowledge about these subpallial neural stem cells and their progeny, focusing on the period of neurogenesis. We describe their cell biological features and the extrinsic and intrinsic molecular codes that guide their fate specification in defined temporal and spatial sequences. We also discuss the role of clonal lineage in the organization and specification of mature neurons.

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Compromised generation of GABAergic interneurons in the brains ofVax1-/- mice

Cited by 52 publications

References 66 publications

Inactivation ofArx, the Murine Ortholog of the X-Linked Lissencephaly with Ambiguous Genitalia Gene, Leads to Severe Disorganization of the Ventral Telencephalon with Impaired Neuronal Migration and Differentiation

Inactivation ofArx, the Murine Ortholog of the X-Linked Lissencephaly with Ambiguous Genitalia Gene, Leads to Severe Disorganization of the Ventral Telencephalon with Impaired Neuronal Migration and Differentiation

Defective Postnatal Neurogenesis and Disorganization of the Rostral Migratory Stream in Absence of theVax1Homeobox Gene

Radial glia in the ventral telencephalon

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