Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system

Hallonet, Marc; Hollemann, Thomas; Pieler, Tomas; Gruß, Peter

doi:10.1101/gad.13.23.3106

Cited by 202 publications

(209 citation statements)

References 47 publications

(35 reference statements)

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“…Our data indicate that TGIF can repress the expression of genes expressed in more dorsal domains of the spinal cord, but does not affect the expression of genes in more ventral regions. It is of interest that defective dorsal-ventral telencephalic patterning resulting in loss of ventral cell types may be associated with HPE (Chiang et al, 1996;Kimura et al, 1996;Golden et al, 1999;Goodrich et al, 1999;Hallonet et al, 1999;Zhang et al, 2001). However, there are several limitations in extrapolating results seen in the spinal cord to possible events in the prosencephalon.…”

Section: Tgif and Holoprosencephalymentioning

confidence: 99%

TGIF, a gene associated with human brain defects, regulates neuronal development

2006

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-TG-3 -interacting factor (TGIF) is an atypical homeodomain protein.In vitro studies have shown that TGIF can repress transcription mediated by either of two signaling pathways: TGF-␤ and retinoic acid signaling. Mutations in TGIF have been detected in patients with holoprosencephaly (HPE), a severe brain malformation associated with mental retardation. Thus, TGIF must play an essential role in nervous system development. However, the precise function of TGIF during vertebrate neural development is unknown. To investigate the in vivo role of TGIF, we overexpressed TGIF in the developing chick neural tube. Overexpressed TGIF decreased expression of specific genes expressed in dorsally restricted domains of the neural tube, including Cath1, Msx2, Pax6, and Wnt1. In contrast, the expression of other transcription factors, including those necessary for ventral fate such as Nkx2.2, was not affected. Furthermore, a missense mutation in TGIF identified in an HPE patient disrupted the activity of TGIF. In addition, the related protein TGIF2 did not demonstrate the same activity as TGIF. Our data suggest that TGIF plays an important role in regulating the expression of genes expressed in specific dorsal-ventral domains during neural development.

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Section: Tgif and Holoprosencephalymentioning

confidence: 99%

TGIF, a gene associated with human brain defects, regulates neuronal development

2006

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“…Detailed expression studies and functional analyses support a direct or indirect role for some of these patterning genes in the formation or the refinement of axon trajectories Mastick et al, 1997;Ba-Charvet et al, 1998;Bertuzzi et al, 1999;Hallonet et al, 1999;Hjorth and Key, 2001). The cues controlling the location and size of the first differentiation clusters have been comparatively less well studied.…”

Section: Introductionmentioning

confidence: 99%

Selective control of neuronal cluster size at the forebrain/midbrain boundary by signaling from the prechordal plate

Tallafuß

Adolf

Bally‐Cuif

2003

Developmental Dynamics

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Within the vertebrate embryonic neural plate, the first neuronal clusters often differentiate at the border of patterning identities. Whether the information inherent in the intersection of patterning identities alone controls all aspects of neuronal cluster development (location, identity, and size) is unknown. Here, we focus on the cluster of the medial longitudinal fascicle (nMLF) and posterior commissure (nPC), located at the forebrain/midbrain (fore/mid) boundary, to address this issue. We first identify expression of the transcription factor Six3 as a common and distinct molecular signature of nMLF and nPC neurons in zebrafish, and we use this marker to monitor mechanisms controlling the location and number of nMLF/nPC neurons. We demonstrate that six3 expression is induced at the fore/mid boundary in pax2.1/no-isthmus and smoothened/slow muscle omitted mutants, where identities adjacent to the six3 cluster are altered; however, in these mutants, the subpopulation of six3-positive cells located within the mispatterned territory is reduced. These results show that induction of the six3 cluster is triggered by the information derived from the intersection in patterning identities alone, whereas correct cluster size depends, in a modular manner, on the identities themselves. The size of the six3 cluster is also controlled independently of neural tube patterning: we demonstrate that the prechordal plate (PCP) is impaired in mixer/bonnie and clyde mutants and that this phenotype secondarily results in an increased production of six3-positive cells at the fore/mid boundary, without correlatively affecting patterning in this area. Thus, a signaling process originating from the PCP distinguishes between neural patterning and the control of six3 cluster size at the fore/mid junction in vivo. Together, our results suggest that a combination of patterning-related and -unrelated mechanisms specifically controls the size of individual early neuronal clusters within the anterior neural plate. Developmental Dynamics 227:524 -535, 2003.

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“…Two genes are located in close vicinity to this region: KIAA1598 (40 kb centromeric) and VAX1 (ventral anterior homeobox 1; 53 kb telomeric). Mice with homozygous Vax1 mutations display craniofacial malformations including cleft palate 6 . Two individuals with a 10q termi nal deletion syndrome with breakpoints in 10q25 have been reported, one with a submucous cleft palate 7 and the other with a cleft lip 8 .…”

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confidence: 99%

Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate

et al. 2009

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We conducted a genome-wide association study for nonsyndromic cleft lip with or without cleft palate (NSCL/P) in 401 affected individuals and 1,323 controls, with replication in an independent sample of 793 NSCL/P triads. We report two new loci associated with NSCL/P at 17q22 (rs227731, combined P = 1.07 × 10 −8 , relative risk in homozygotes = 1.84, 95% CI 1.34-2.53) and 10q25.3 (rs7078160, combined P = 1.92 × 10 −8 , relative risk in homozygotes = 2.17, 95% CI 1.32-3.56).NSCL/P is one of the most common human birth defects. In European populations, NSCL/P has a prevalence ranging from 1 in 700 to 1 in 1,000. We recently reported a susceptibility locus for NSCL/P at chromo some 8q24.21 from a genome wide association study in 224 individuals with NSCL/P (cases) and 383 population based controls 1 . This locus is the second susceptibility locus to have been unequivocally identified for NSCL/P to date, the first being the IRF6 locus 2 .To identify additional cleft susceptibility loci, we enlarged our sample by genotyping an additional set of 177 NSCL/P cases and adding the genotypes of 940 population based controls of central European origin. Genotyping was performed using Illumina BeadChips (Human610 Quad and HumanHap 550k).Following quality control (Supplementary Methods and Supplementary Fig. 1), association analysis of 521,288 SNPs having a minor allele frequency (MAF) of ≥1% in controls was performed in 399 cases and 1,318 controls.After excluding markers from the previously described 8q24.21 locus, 20 SNPs with P < 10 −5 remained. Five chromosomal loci (8q12.3, 10q25.3, 13q31.1, 15q13.3 and 17q22) were located within these 20 top SNPs, and the associations at these loci were further supported by at least three more SNPs with P < 10 −4 ( Supplementary Fig. 2 and Supplementary Table 1). Two additional regions were considered to be promising NSCL/P susceptibility loci (6p22.1, 11q14.2), as they contained at least four markers with P < 10 −4 .To replicate the genome wide association study (GWAS) findings, we selected the 20 top SNPs (P < 10 −5 ) as well as additional backup markers for each of the seven previously mentioned loci, resulting in two replication assays. We included additional SNPs with P < 10 −4 in the two replication assays, giving highest priority to SNPs with the lowest P values. Thus, a total of 56 markers were genotyped in a replication sample of 793 NSCL/P triads of European origin. Genotyping using matrix assisted laser desorption/ionization time of flight (MALDI TOF) mass spectrometry (Sequenom Inc.) was successful for 45 markers (representing 32 different loci), which were then analyzed by the transmission disequilibrium test in 665 triads (128 triads were excluded after quality control, Supplementary Methods).Of the 45 SNPs successfully genotyped, 11 (representing six differ ent loci) showed P < 0.05 in the replication sample (Supplementary Table 2). Two of these SNPs remained significant after correction for multiple testing by a conservative Bonferroni procedure (17q22: rs227731, P corr ...

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Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system

Abstract: The novel homeobox-containing gene

Cited by 202 publications

References 47 publications

TGIF, a gene associated with human brain defects, regulates neuronal development

TGIF, a gene associated with human brain defects, regulates neuronal development

Selective control of neuronal cluster size at the forebrain/midbrain boundary by signaling from the prechordal plate

Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate

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