Genomes and Genes
Gene Symbol: Dlx2
Description: distal-less homeobox 2
Alias: AW121999, Dlx-2, Tes-1, homeobox protein DLX-2, DII A, homeobox protein TES-1
- Thomas B, Tucker A, Qui M, Ferguson C, Hardcastle Z, Rubenstein J, et al. Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition. Development. 1997;124:4811-8 pubmed..This is the first indication that the development of different shaped teeth at different positions in the jaws is determined by independent genetic pathways. ..
- Toresson H, Potter S, Campbell K. Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2. Development. 2000;127:4361-71 pubmed
- Tavares A, Garcia E, Kuhn K, Woods C, Williams T, Clouthier D. Ectodermal-derived Endothelin1 is required for patterning the distal and intermediate domains of the mouse mandibular arch. Dev Biol. 2012;371:47-56 pubmed publisher..Together, our results illustrate an integral role for ectoderm-derived Edn1 in early arch morphogenesis, particularly in the intermediate domain...
- Peters H, Balling R. Teeth. Where and how to make them. Trends Genet. 1999;15:59-65 pubmed..This cascade provides a molecular model by which reciprocal tissue interactions are controlled. ..
- Le T, Du G, Fonseca M, Zhou Q, Wigle J, Eisenstat D. Dlx homeobox genes promote cortical interneuron migration from the basal forebrain by direct repression of the semaphorin receptor neuropilin-2. J Biol Chem. 2007;282:19071-81 pubmedDlx homeobox genes play an important role in vertebrate forebrain development. Dlx1/Dlx2 null mice die at birth with an abnormal cortical phenotype, including impaired differentiation and migration of GABAergic interneurons to the ..
- Cobos I, Broccoli V, Rubenstein J. The vertebrate ortholog of Aristaless is regulated by Dlx genes in the developing forebrain. J Comp Neurol. 2005;483:292-303 pubmed..Therefore, our results suggest evolutionarily conserved functions of Dlx genes in regulating Arx expression between Drosophila and vertebrates. ..
- Yun K, Potter S, Rubenstein J. Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon. Development. 2001;128:193-205 pubmed..The role of Pax6 in dorsalizing the telencephalon is similar to its role in the spinal cord, supporting the hypothesis that some dorsoventral patterning mechanisms are used at all axial levels of the central nervous system. ..
- Murashima Suginami A, Takahashi K, Sakata T, Tsukamoto H, Sugai M, Yanagita M, et al. Enhanced BMP signaling results in supernumerary tooth formation in USAG-1 deficient mouse. Biochem Biophys Res Commun. 2008;369:1012-6 pubmed publisher..BMP signaling in the rudimentary maxillary incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad protein, was significantly enhanced...
- Sato T, Kurihara Y, Asai R, Kawamura Y, Tonami K, Uchijima Y, et al. An endothelin-1 switch specifies maxillomandibular identity. Proc Natl Acad Sci U S A. 2008;105:18806-11 pubmed publisher..Also, we show that, within PA1, CNCCs are competent to form both mandibular and maxillary structures and that an Edn1 switch is responsible for the choice of either morphogenetic program. ..
- McGuinness T, Porteus M, Smiga S, Bulfone A, Kingsley C, Qiu M, et al. Sequence, organization, and transcription of the Dlx-1 and Dlx-2 locus. Genomics. 1996;35:473-85 pubmed..The sequence of the human Dlx-2 gene is reported and is compared to that of the murine gene. Finally, sequence analysis of the deduced protein sequences reveals several candidate functional domains. ..
- Sussel L, Marin O, Kimura S, Rubenstein J. Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development. 1999;126:3359-70 pubmed..TrkA-positive neurons (probable cholinergic neurons) and has reduced numbers of cortical cells expressing GABA, DLX2 and calbindin that migrate from the pallidum through the striatum and into the cortex...
- Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen M, et al. Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism. Mol Cell Biol. 1997;17:2920-32 pubmed..Finally, we show that the expression patterns of representative Msx and Dlx genes (Msx1, Msx2, Dlx2, and Dlx5) overlap in mouse embryogenesis during limb bud and craniofacial development, consistent with the ..
- Marin O, Yaron A, Bagri A, Tessier Lavigne M, Rubenstein J. Sorting of striatal and cortical interneurons regulated by semaphorin-neuropilin interactions. Science. 2001;293:872-5 pubmed
- Pleasure S, Anderson S, Hevner R, Bagri A, Marin O, Lowenstein D, et al. Cell migration from the ganglionic eminences is required for the development of hippocampal GABAergic interneurons. Neuron. 2000;28:727-40 pubmed..Loss of hippocampal interneurons does not appear to have major effects on the early development of hippocampal projection neurons nor on the pathfinding of afferrent tracts. ..
- Saino Saito S, Berlin R, Baker H. Dlx-1 and Dlx-2 expression in the adult mouse brain: relationship to dopaminergic phenotypic regulation. J Comp Neurol. 2003;461:18-30 pubmed..The widespread expression of Dlx mRNA and protein in the adult brain suggests that these genes may have additional roles in mature animals. ..
- Qiu M, Bulfone A, Martinez S, Meneses J, Shimamura K, Pedersen R, et al. Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the forebrain. Genes Dev. 1995;9:2523-38 pubmed..These results show that Dlx-2 controls development of the branchial arches and the forebrain and suggests its role in craniofacial evolution. ..
- Zhao X, Zhang Z, Song Y, Zhang X, Zhang Y, Hu Y, et al. Transgenically ectopic expression of Bmp4 to the Msx1 mutant dental mesenchyme restores downstream gene expression but represses Shh and Bmp2 in the enamel knot of wild type tooth germ. Mech Dev. 2000;99:29-38 pubmed..of a Bmp4 transgene driven by the mouse Msx1promoter in the dental mesenchyme restored the expression of Lef-1 and Dlx2 but neither Fgf3 nor syndecan-1 in the Msx1 mutant molar tooth germ...
- Feng J, Bi C, Clark B, Mady R, Shah P, Kohtz J. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev. 2006;20:1470-84 pubmed
- Anderson S, Qiu M, Bulfone A, Eisenstat D, Meneses J, Pedersen R, et al. Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons. Neuron. 1997;19:27-37 pubmed..Several lines of evidence suggest that mutations in Dlx-1 and Dlx-2 produce abnormalities in the development of the striatal subventricular zone and in the differentiation of striatal matrix neurons. ..
- Cobos I, Long J, Thwin M, Rubenstein J. Cellular patterns of transcription factor expression in developing cortical interneurons. Cereb Cortex. 2006;16 Suppl 1:i82-8 pubmed..in differentiating and mature neocortical interneurons of 8 transcription factors, including 6 homeobox (Dlx1, Dlx2, Dlx5, Arx, Lhx6, Cux2), 1 basic helix-loop-helix, (NPAS1), and 1 bZIP (MafB)...
- Xu Q, Cobos I, De La Cruz E, Rubenstein J, Anderson S. Origins of cortical interneuron subtypes. J Neurosci. 2004;24:2612-22 pubmed..By establishing spatial differences in the origins of interneuron subtypes, these studies lay the groundwork for elucidating the molecular bases for their distinct differentiation pathways. ..
- Gutin G, Fernandes M, Palazzolo L, Paek H, Yu K, Ornitz D, et al. FGF signalling generates ventral telencephalic cells independently of SHH. Development. 2006;133:2937-46 pubmed..Moreover, the Fgfr1;Fgfr2 phenotype, unlike the Shh phenotype, is not rescued by loss of Gli3, further indicating that FGFs act downstream of Shh and Gli3 to generate ventral telencephalic cell types. ..
- Trumpp A, Depew M, Rubenstein J, Bishop J, Martin G. Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch. Genes Dev. 1999;13:3136-48 pubmed..Because the mutant mice resemble humans with first arch syndromes that include agnathia, our results raise the possibility that some of these syndromes are caused by mutations that affect FGF8 signaling in BA1 ectoderm...
- Poitras L, Ghanem N, Hatch G, Ekker M. The proneural determinant MASH1 regulates forebrain Dlx1/2 expression through the I12b intergenic enhancer. Development. 2007;134:1755-65 pubmed..In the developing forebrain of mammals, the combined function of the Dlx1, Dlx2, Dlx5 and Dlx6 homeobox genes is necessary for the differentiation of the GABAergic interneurons born in the ..
- Kuwajima T, Nishimura I, Yoshikawa K. Necdin promotes GABAergic neuron differentiation in cooperation with Dlx homeodomain proteins. J Neurosci. 2006;26:5383-92 pubmed..Immunohistochemical analysis revealed that necdin was coexpressed with Dlx2, Dlx5, or MAGE-D1 in a subpopulation of embryonic forebrain cells...
- Colombo E, Galli R, Cossu G, Gecz J, Broccoli V. Mouse orthologue of ARX, a gene mutated in several X-linked forms of mental retardation and epilepsy, is a marker of adult neural stem cells and forebrain GABAergic neurons. Dev Dyn. 2004;231:631-9 pubmed..and is enhanced during differentiation of the subpallial structures of the ganglionic eminences, overlapping with Dlx2, Dlx5, and Gad1 transcriptional domains...
- Vyas A, Saha B, Lai E, Tole S. Paleocortex is specified in mice in which dorsal telencephalic patterning is severely disrupted. J Comp Neurol. 2003;466:545-53 pubmed..Furthermore, our in vitro data reveal that, if mechanisms outside the lateral telencephalon are involved in the specification of the paleocortex, they must act extremely early, prior to E10.5. ..
- Liu J, Ghattas I, Liu S, Chen S, Rubenstein J. Dlx genes encode DNA-binding proteins that are expressed in an overlapping and sequential pattern during basal ganglia differentiation. Dev Dyn. 1997;210:498-512 pubmed..Antisense Dlx-1 and -6 have their highest expression in the SVZ. These results suggest that each of these Dlx genes may have a distinct role in different steps of differentiation in the basal ganglia. ..
- Anderson S, Eisenstat D, Shi L, Rubenstein J. Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science. 1997;278:474-6 pubmed..Finally, mice lacking the homeodomain proteins DLX-1 and DLX-2 show no detectable cell migration from the subcortical telencephalon to the neocortex and also have few GABA-expressing cells in the neocortex. ..
- Carney R, Cocas L, Hirata T, Mansfield K, Corbin J. Differential regulation of telencephalic pallial-subpallial boundary patterning by Pax6 and Gsh2. Cereb Cortex. 2009;19:745-59 pubmed publisher..Thus, in addition to their well-characterized cross-repressive roles in dorsal/ventral patterning our analyses reveal important novel functions of Gsh2 and Pax6 in the regulation of PSB progenitor pool specification and patterning. ..
- Potter G, Petryniak M, Shevchenko E, McKinsey G, Ekker M, Rubenstein J. Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons. Mol Cell Neurosci. 2009;40:167-86 pubmed publisherDLX1 and DLX2 transcription factors are necessary for forebrain GABAergic neuron differentiation, migration, and survival...
- Brill M, Snapyan M, Wohlfrom H, Ninkovic J, Jawerka M, Mastick G, et al. A dlx2- and pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb. J Neurosci. 2008;28:6439-52 pubmed publisher..Here we show that in the adult brain, Dlx 1 and Dlx2 are expressed in progenitors of the lateral but not the dorsal subependymal zone (SEZ), thus exhibiting a striking ..
- Grigoriou M, Tucker A, Sharpe P, Pachnis V. Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development. Development. 1998;125:2063-74 pubmed..We suggest that Fgf8 and Lhx6 and Lhx7 are key components of signalling cascades which determine morphogenesis and differentiation in the first branchial arch and the basal forebrain. ..
- Nery S, Fishell G, Corbin J. The caudal ganglionic eminence is a source of distinct cortical and subcortical cell populations. Nat Neurosci. 2002;5:1279-87 pubmed..Moreover, we report that the migratory fate of cells from the CGE is intrinsically determined by embryonic day 13.5 (E13.5). Together, these results provide the first insights into the development and fate of the CGE. ..
- Flames N, Pla R, Gelman D, Rubenstein J, Puelles L, Marin O. Delineation of multiple subpallial progenitor domains by the combinatorial expression of transcriptional codes. J Neurosci. 2007;27:9682-95 pubmed..Furthermore, the results of microtransplantation experiments in vivo corroborate that anatomically defined regions of the mouse subpallium, such as the medial ganglionic eminence, can be subdivided into functionally distinct domains. ..
- Cobos I, Calcagnotto M, Vilaythong A, Thwin M, Noebels J, Baraban S, et al. Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nat Neurosci. 2005;8:1059-68 pubmed..Dlx1 mutant mice show generalized electrographic seizures and histological evidence of seizure-induced reorganization, linking the Dlx1 mutation to delayed-onset epilepsy associated with interneuron loss. ..
- Porteus M, Bulfone A, Ciaranello R, Rubenstein J. Isolation and characterization of a novel cDNA clone encoding a homeodomain that is developmentally regulated in the ventral forebrain. Neuron. 1991;7:221-9 pubmed..Within the central nervous system of the midgestation mouse embryo, it is expressed exclusively in the ventral forebrain. It is likely that Tes-1 plays a regulatory role in the development of this complex neural structure. ..
- Anderson S, Marin O, Horn C, Jennings K, Rubenstein J. Distinct cortical migrations from the medial and lateral ganglionic eminences. Development. 2001;128:353-63 pubmed..In addition, by comparing the phenotypes of mouse mutants with differential effects on MGE and LGE migration, we provide evidence that the MGE and LGE may give rise to different subtypes of cortical interneurons. ..
- Stühmer T, Anderson S, Ekker M, Rubenstein J. Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression. Development. 2002;129:245-52 pubmed..This approach showed that ectopic expression of Dlx2 and Dlx5 induced the expression of glutamic acid decarboxylases (GADs), the enzymes that synthesize GABA...
- Zhou Q, Le T, Qiu X, Spencer V, de Melo J, Du G, et al. Identification of a direct Dlx homeodomain target in the developing mouse forebrain and retina by optimization of chromatin immunoprecipitation. Nucleic Acids Res. 2004;32:884-92 pubmed..Dlx genes are expressed in the developing forebrain, retina, craniofacial structures and limbs. Dlx1/Dlx2 double knockout mice die at birth with multiple defects including abnormal forebrain development and decreased Dlx5 ..
- Thesleff I, Sharpe P. Signalling networks regulating dental development. Mech Dev. 1997;67:111-23 pubmed
- Depew M, Lufkin T, Rubenstein J. Specification of jaw subdivisions by Dlx genes. Science. 2002;298:381-5 pubmed..We suggest that nested Dlx expression in the arches patterns their proximodistal axes. Evolutionary acquisition and subsequent refinement of jaws may have been dependent on modification of Dlx expression. ..
- Abu Issa R, Smyth G, Smoak I, Yamamura K, Meyers E. Fgf8 is required for pharyngeal arch and cardiovascular development in the mouse. Development. 2002;129:4613-25 pubmed..This study defines the cardiovascular defects present in Fgf8 mutants and supports a role for Fgf8 in development of all the pharyngeal arches and in NCC survival. ..
- Zerucha T, Stühmer T, Hatch G, Park B, Long Q, Yu G, et al. A highly conserved enhancer in the Dlx5/Dlx6 intergenic region is the site of cross-regulatory interactions between Dlx genes in the embryonic forebrain. J Neurosci. 2000;20:709-21 pubmedFour Dlx homeobox genes, Dlx1, Dlx2, Dlx5, and Dlx6 are expressed in the same primordia of the mouse forebrain with temporally overlapping patterns...
- Sheehy N, Cordes K, White M, Ivey K, Srivastava D. The neural crest-enriched microRNA miR-452 regulates epithelial-mesenchymal signaling in the first pharyngeal arch. Development. 2010;137:4307-16 pubmed publisher..Dicer mutant embryos had reduced expression of Dlx2, a transcriptional regulator of pharyngeal arch development, in the first pharyngeal arch (PA1)...
- Qiu M, Bulfone A, Ghattas I, Meneses J, Christensen L, Sharpe P, et al. Role of the Dlx homeobox genes in proximodistal patterning of the branchial arches: mutations of Dlx-1, Dlx-2, and Dlx-1 and -2 alter morphogenesis of proximal skeletal and soft tissue structures derived from the first and second arches. Dev Biol. 1997;185:165-84 pubmed..Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates. ..
- Bulfone A, Wang F, Hevner R, Anderson S, Cutforth T, Chen S, et al. An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons. Neuron. 1998;21:1273-82 pubmed..These observations suggest that the establishment of a topographic map is not dependent upon cues provided by, or synapse formation with, the major neuronal cell types in the olfactory bulb. ..
- Assimacopoulos S, Grove E, Ragsdale C. Identification of a Pax6-dependent epidermal growth factor family signaling source at the lateral edge of the embryonic cerebral cortex. J Neurosci. 2003;23:6399-403 pubmed..We find that the antihem is lost in mice homozygous for the Small eye (Pax6) mutation and suggest the loss of EGF signaling at least partially explains defects in cortical patterning and cell migration in Small eye mice. ..
- Bei M, Maas R. FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development. Development. 1998;125:4325-33 pubmed..In addition, we have investigated the effects of FGFs and BMP4 on the distal-less homeobox genes Dlx1 and Dlx2 and we have clarified the relationship between Msx and Dlx gene function in the developing tooth...
- Ruest L, Xiang X, Lim K, Levi G, Clouthier D. Endothelin-A receptor-dependent and -independent signaling pathways in establishing mandibular identity. Development. 2004;131:4413-23 pubmed..Together, our results suggest that the establishment of a 'mandibular identity' during lower jaw development requires both Ednra-dependent and -independent signaling pathways. ..
- Corbin J, Gaiano N, Machold R, Langston A, Fishell G. The Gsh2 homeodomain gene controls multiple aspects of telencephalic development. Development. 2000;127:5007-20 pubmed..Taken together, our data support a model in which Gsh2, in response to sonic hedgehog signaling, plays a crucial role in multiple aspects of telencephalic development. ..
- Toresson H, Mata De Urquiza A, Fagerstrom C, Perlmann T, Campbell K. Retinoids are produced by glia in the lateral ganglionic eminence and regulate striatal neuron differentiation. Development. 1999;126:1317-26 pubmed..These findings, therefore, strongly support the notion that local retinoid signalling within the lateral ganglionic eminence regulates striatal neuron differentiation. ..
- Eisenstat D, Liu J, Mione M, Zhong W, Yu G, Anderson S, et al. DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation. J Comp Neurol. 1999;414:217-37 pubmed..In the basal telencephalon, these DLX-positive cells differentiate into projection neurons of the striatum and pallidum as well as interneurons, some of which migrate to the cerebral cortex and the olfactory bulb. ..
- Cobos I, Borello U, Rubenstein J. Dlx transcription factors promote migration through repression of axon and dendrite growth. Neuron. 2007;54:873-88 pubmed..In Dlx1-/-;Dlx2-/- mutants, neurite length is increased and cells fail to migrate...
- Bulchand S, Grove E, Porter F, Tole S. LIM-homeodomain gene Lhx2 regulates the formation of the cortical hem. Mech Dev. 2001;100:165-75 pubmed..The defect in the Lhx2-/- telencephalon appears to be at this step. ..