Distinct<i>cis</i>-Regulatory Elements from the<i>Dlx1/Dlx2</i>Locus Mark Different Progenitor Cell Populations in the Ganglionic Eminences and Different Subtypes of Adult Cortical Interneurons

Ghanem, Noël; Yu, Man; Long, Jason E.; Hatch, Gary; Rubenstein, John L.R.; Ekker, Marc

doi:10.1523/jneurosci.4725-06.2007

Cited by 105 publications

(137 citation statements)

References 37 publications

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…The Dlx1/Dlx2 enhancer I12b contains putative E2F binding sites acting as repressor sites in vivo The transcription of Dlx genes in the forebrain is regulated primarily by highly conserved tissue-specific enhancers that act as cis-regulatory elements shared between the two Dlx genes belonging to one cluster (Zerucha et al, 2000;Ghanem et al, 2003Ghanem et al, , 2007. Given the significant reduction in Dlx1 and Dlx2 expressions in the absence of Rb, we examined the mechanism by which Rb may mediate the regulation of the Dlx1/Dlx2 bigene cluster.…”

Section: Rb Is Required For the Proper Maturation And Migration Of Obmentioning

confidence: 99%

“…This enhancer is particularly important because it controls Dlx expression in subpopulation(s) of interneurons that migrate to the dorsal cortex and OB. Furthermore, the enhancer activity is known to be high specifically in the ventral telencephalic regions severely affected by the absence of Rb (Ferguson et al, 2002;Ghanem et al, 2007;Batista-Brito et al, 2008). To test this possibility in vivo, we first generated Rb conditional mutants carrying LacZ reporter genes under the control of the human ␤-globin minimal promoter and the Dlx1/2-I12b enhancer (I12b-LacZ).…”

Section: Rb Is Required For the Proper Maturation And Migration Of Obmentioning

confidence: 99%

“…Since Dlx gene transcription is partially controlled by the forebrain-specific enhancer, I12b (Zerucha et al, 2000;Ghanem et al, 2003Ghanem et al, , 2007, we searched I12b for classical E2F consensus sites. Three putative E2F sites were identified in the enhancer, which we called A, B, and C ( Fig.…”

Section: Rb Is Required For the Proper Maturation And Migration Of Obmentioning

confidence: 99%

See 2 more Smart Citations

The Rb/E2F Pathway Modulates Neurogenesis through Direct Regulation of the Dlx1/Dlx2 Bigene Cluster

Ghanem¹,

Andrusiak²,

Svoboda³

et al. 2012

Journal of Neuroscience

Self Cite

View full text Add to dashboard Cite

During brain morphogenesis, the mechanisms through which the cell cycle machinery integrates with differentiation signals remain elusive. Here we show that the Rb/E2F pathway regulates key aspects of differentiation and migration through direct control of the Dlx1 and Dlx2 homeodomain proteins, required for interneuron specification. Rb deficiency results in a dramatic reduction of Dlx1 and Dlx2 gene expression manifested by loss of interneuron subtypes and severe migration defects in the mouse brain. The Rb/E2F pathway modulates Dlx1/Dlx2 regulation through direct interaction with a Dlx forebrain-specific enhancer, I12b, and the Dlx1/Dlx2 proximal promoter regions, through repressor E2F sites both in vitro and in vivo. In the absence of Rb, we demonstrate that repressor E2Fs inhibit Dlx transcription at the Dlx1/Dlx2 promoters and Dlx1/2-I12b enhancer to suppress differentiation. Our findings support a model whereby the cell cycle machinery not only controls cell division but also modulates neuronal differentiation and migration through direct regulation of the Dlx1/Dlx2 bigene cluster during embryonic development.

show abstract

Section: Rb Is Required For the Proper Maturation And Migration Of Obmentioning

confidence: 99%

Section: Rb Is Required For the Proper Maturation And Migration Of Obmentioning

confidence: 99%

Section: Rb Is Required For the Proper Maturation And Migration Of Obmentioning

confidence: 99%

See 1 more Smart Citation

The Rb/E2F Pathway Modulates Neurogenesis through Direct Regulation of the Dlx1/Dlx2 Bigene Cluster

Ghanem¹,

Andrusiak²,

Svoboda³

et al. 2012

Journal of Neuroscience

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, GABA neurons of the basal forebrain are not restricted to the compartment of origin but migrate across compartmental boundaries 18,19 , despite expressing compartment-specific homeobox genes 29 . Which of these two models applies to telencephalic endothelial cells?…”

Section: Endothelial Cells Express Homeobox Transcription Factorsmentioning

confidence: 99%

Compartment-specific transcription factors orchestrate angiogenesis gradients in the embryonic brain

et al. 2008

View full text Add to dashboard Cite

Prevailing notions of cerebral vascularization imply that blood vessels sprout passively into the brain parenchyma from pial vascular plexuses to meet metabolic needs of growing neuronal populations. Endothelial cells, building blocks of blood vessels, are thought to be homogeneous in the brain with respect to their origins, gene expression patterns and developmental mechanisms. These current notions that cerebral angiogenesis is regulated by local environmental signals contrast with current models of cell-autonomous regulation of neuronal development. Here we demonstrate that telencephalic angiogenesis in mice progresses in an orderly, ventral-to-dorsal gradient regulated by compartment-specific homeobox transcription factors. Our data offer new perspectives on intrinsic regulation of angiogenesis in the embryonic telencephalon, call for a revision of the current models of telencephalic angiogenesis and support novel roles for endothelial cells in brain development.Brain development is supported by concomitant development of brain vasculature. However, blood vessels or endothelial cells are generally considered to lack molecular diversity in the embryonic or mature CNS 1,2 . Currently, it is believed that once the perineural plexuses on the pial surface (pial vessels) surrounding the neural tube are produced, cerebral vasculature develops further by passive vessel sprouting into the brain parenchyma in response to increased tissue mass and oxygen demand 1,2 . Although classical studies identified a ventral to dorsal temporal developmental angiogenesis gradient in the telencephalon 3 , the sequence of angiogenesis was considered to merely shadow neurogenesis and neuronal maturation. Similarly, although shared mechanisms regulating vascular and neuronal development have been recognized 4 , the canonical principles of neuronal development are not seen as applicable to CNS angiogenesis.

show abstract

“…To circumvent this issue, we developed a conditional deletion of Dlx1 restricted to forebrain GABAergic neurons using a floxed conditional allele of Dlx1 and DlxI12b-Cre (I12b-Cre). DlxI12b is an enhancer element of Dlx1 (40,41). By placing Cre-recombinase under the control of this enhancer, which is not expressed in the primordia of the middle ear, recombination occurs in 95% of cortical interneurons (41).…”

mentioning

confidence: 99%

Chronic reduction in inhibition reduces receptive field size in mouse auditory cortex

Seybold

Stanco

Cho³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Inhibitory interneurons regulate the responses of cortical circuits. In auditory cortical areas, inhibition from these neurons narrows spectral tuning and shapes response dynamics. Acute disruptions of inhibition expand spectral receptive fields. However, the effects of long-term perturbations of inhibitory circuitry on auditory cortical responses are unknown. We ablated ∼30% of dendrite-targeting cortical inhibitory interneurons after the critical period by studying mice with a conditional deletion of Dlx1. Following the loss of interneurons, baseline firing rates rose and tone-evoked responses became less sparse in auditory cortex. However, contrary to acute blockades of inhibition, the sizes of spectral receptive fields were reduced, demonstrating both higher thresholds and narrower bandwidths. Furthermore, long-latency responses at the edge of the receptive field were absent. On the basis of changes in response dynamics, the mechanism for the reduction in receptive field size appears to be a compensatory loss of corticocortically (CC) driven responses. Our findings suggest chronic conditions that feature changes in inhibitory circuitry are not likely to be well modeled by acute network manipulations, and compensation may be a critical component of chronic neuronal conditions. P rocessing of auditory information in the auditory cortex underlies the conscious perception of sound and speech comprehension. Inhibitory interneurons, representing ∼20% of cortical neurons (1), regulate this processing by shaping the spectral tuning (2-13), temporal tuning (14-16), and response dynamics of local excitatory neurons (5-11). Inhibitory interneurons form multiple subtypes on the basis of morphology, physiology, and biochemistry (1, 17) that likely serve distinct roles in cortical processing.Loss of inhibitory interneurons is observed in conditions that affect cortical processing in humans, and in animal models of human disorders, including aging (18, 19), autism (20), schizophrenia (21-23), traumatic brain injury (TBI) (24), hearing loss (25-28), and tinnitus (29). Often, a particular disease is associated with a specific deficit in a subset of interneurons. For example, rodent models of autism demonstrate a loss of parvalbumin positive (PV + ) interneurons (20), whereas aging and TBI models show a greater loss of somatostatin (SST) + interneurons than other interneuron populations (19,24). The disruption of specific interneuron populations may underlie the particular cognitive defects associated with each condition. Therefore, it is necessary to understand the effects following chronic reductions of particular interneuron subtypes.One mouse model of an adult-onset loss of dendrite-targeting interneurons (DTIs) is the Dlx1 mutant (30). Dlx1 encodes a homeobox transcription factor from the Dlx family that regulates the development, migration, and survival of cortical interneurons (30-32). In Dlx1 mutants, the other Dlx family members compensate for the deficiency and thereby allow interneurons to migrate into cortex (30)....

show abstract

Distinctcis-Regulatory Elements from theDlx1/Dlx2Locus Mark Different Progenitor Cell Populations in the Ganglionic Eminences and Different Subtypes of Adult Cortical Interneurons

Cited by 105 publications

References 37 publications

The Rb/E2F Pathway Modulates Neurogenesis through Direct Regulation of the Dlx1/Dlx2 Bigene Cluster

The Rb/E2F Pathway Modulates Neurogenesis through Direct Regulation of the Dlx1/Dlx2 Bigene Cluster

Compartment-specific transcription factors orchestrate angiogenesis gradients in the embryonic brain

Chronic reduction in inhibition reduces receptive field size in mouse auditory cortex

Contact Info

Product

Resources

About