Exclusion of genes from the EYA‐DACH‐SIX‐PAX pathway as candidates for Branchio–Oculo–Facial syndrome (BOFS)

Kaiser, René; Posteguillo, Elena Guillén; Müller, Dietmar; Just, Walter

doi:10.1002/ajmg.a.31875

Cited by 11 publications

(9 citation statements)

References 23 publications

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“…The use of the hth-eya-so-dac cassette seems to be evolutionarily conserved, as genes of the Pax, Six, Eya, Dach and, in some instances, Meis gene families have been shown to be co-expressed and functional during the development of many different organ types in vertebrates: from eyes, sensory placodes or brain regions to muscle, kidney or pancreas (Ikeda et al, 2002;Zhang et al, 2002Zhang et al, , 2006Li et al, 2003;Bessarab et al, 2004;Purcell et al, 2005;Bumsted-O'Brien et al, 2007;Kaiser et al, 2007;Erickson et al, 2010;Santos et al, 2011). Therefore, further study of the early development of the Drosophila lamina might shed light on the general mechanisms governed by this multipurpose genetic cassette in vertebrates.…”

Section: Discussionmentioning

confidence: 99%

A conserved transcriptional network regulates lamina development in the Drosophila visual system

2014

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The visual system of insects is a multilayered structure composed externally by the compound eye and internally by the three ganglia of the optic lobe: lamina, medulla and the lobula complex. The differentiation of lamina neurons depends heavily on Hedgehog (Hh) signaling, which is delivered by the incoming photoreceptor axons, and occurs in a wave-like fashion. Despite the primary role of lamina neurons in visual perception, it is still unclear how these neurons are specified from neuroepithelial (NE) progenitors. Here we show that a homothorax (hth)-eyes absent (eya)-sine oculis (so)-dachshund (dac) gene regulatory cassette is involved in this specification. Lamina neurons differentiate from NE progenitors that express hth, eya and so. One of the first events in the differentiation of lamina neurons is the upregulation of dac expression in response to Hh signaling. We show that this dac upregulation, which marks the transition from NE progenitors into lamina precursors, also requires Eya/So, the expression of which is locked in by mutual feedback. dac expression is crucial for lamina differentiation because it ensures repression of hth, a negative regulator of single-minded, and thus dac allows further lamina neuron differentiation. Therefore, the specification of lamina neurons is controlled by coupling the cell-autonomous hth-eya-so-dac regulatory cassette to Hh signaling.

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Section: Discussionmentioning

confidence: 99%

A conserved transcriptional network regulates lamina development in the Drosophila visual system

2014

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“…Mutations in human Six1 are a major underlying cause of branchio-oto-renal (BOR) syndrome [97, 98]. However, Six1 lesions are specifically excluded from Branchio-oculo-facial (BOF) syndrome even though both syndromes share many phenotypic features [99]. Interestingly, the evidence points to members of the Optix subgroup, Six3 and Six6, as being the major SIX proteins in the retina.…”

Section: Six Proteins In Retinal Developmentmentioning

confidence: 99%

The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease

Kumar

2008

Cell. Mol. Life Sci.

224

222

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The sine oculis homeobox (SIX) protein family is a group of evolutionarily conserved transcription factors that are found in diverse organisms that range from flatworms to humans. These factors are expressed within, and play pivotal developmental roles in, cell populations that give rise to the head, retina, ear, nose, brain, kidney, muscle and gonads. Mutations within the fly and mammalian versions of these genes have adverse consequences on the development of these organs/tissues. Several SIX proteins have been shown to directly influence the cell cycle and are present at elevated levels during tumorigenesis and within several cancers. This review aims to highlight aspects of (1) the evolutionary history of the SIX family; (2) the structural differences and similarities amongst the different SIX proteins; (3) the role that these genes play in retinal development; and (4) the influence that these proteins have on cell proliferation and growth. KeywordsSine oculis; optix; DSix4; Drosophila; SIX; mammals; retina; gonad; mesoderm SIX proteins: A family historyMutations within the founding member of the sine oculis homeobox (SIX) family, sine oculis (so), were first identified and characterized in the fruit fly, Drosophila melanogaster at a time when a growing number of mutants affecting the structure, size and pigmentation of the eye were being recovered [1]. Mutations in so proved to be particularly interesting as loss-offunction mutants not only had dramatic effects on the compound eye but also, in fact, adversely affected the entire visual system [2][3][4][5]. Subsequent molecular efforts identified two additional SIX family members, optix and DSix4 in flies [6,7]. optix, like so, is expressed and functions in the developing eye, although its role in the retina appears to be distinct from that of so [7][8][9]. DSix4, on the other hand, plays no role in the eye but instead functions in several mesoderm derivatives including a subset of somatic muscles, the somatic cells of the gonad and the fat body [10,11]. The three SIX genes that are found in Drosophila are thought to have arisen through the duplication of an ancestral SIX gene, an event that occurred prior to the evolution of the Bilateria. Homologs of the so, optix and DSix4 proteins have been identified in a wide range of organisms throughout the animal kingdom. A comparison of gene structures and sequence has led to the creation of three subclasses of SIX proteins: each class contains one of the fly genes and their orthologs ( Fig. 1) [6]. The remarkable demonstration that Pax6 (ey in flies, Sey in mouse, Pax6 in humans) universally governs retinal development across the animal kingdom was a strong impetus to find vertebrate orthologs of the other genes involved in fly retinal specification [12][13][14]. In the immediate years after cloning so from the fruit fly, homologs were quickly identified in a number of vertebrate systems including medaka fish, chickens, frogs, zebrafish, mice and humans [15][16][17][18][19][20][21][22][23][24][25][26][27][...

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“…Presence of a shared haplotype in five affected members of a single BOFS family was reported suggesting linkage to chromosome 6p21.31-p25.32 [Kaiser et al, 2007]. Indeed, the molecular basis of the condition has recently been elucidated thanks to the detection of a deletion of 3.2 Mb on chromosome 6 (6p24.3) in an affected family using 500K SNP microarray analysis .…”

Section: Introductionmentioning

confidence: 99%

Confirmation of TFAP2A gene involvement in branchio‐oculo‐facial syndrome (BOFS) and report of temporal bone anomalies

Riehm

Greene

Pelletier

et al. 2009

American J of Med Genetics Pt A

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Branchio-oculo-facial syndrome (BOFS) is an autosomal-dominant condition characterized by three main features, respectively: branchial defects, ocular anomalies, and craniofacial defects including cleft lip and/or palate (CL/P). We report on one family with three affected, and two sporadic cases that have been found to carry missense mutations in the newly reported BOFS gene: TFAP2A. This report confirms the involvement of this transcription factor in this developmental syndrome with clinical variability. Moreover, we present CT scan temporal bone anomalies in the familial cases, related to branchial arch defects, highlighting the importance of radiological investigations for differential diagnosis.

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Exclusion of genes from the EYA‐DACH‐SIX‐PAX pathway as candidates for Branchio–Oculo–Facial syndrome (BOFS)

Cited by 11 publications

References 23 publications

A conserved transcriptional network regulates lamina development in the Drosophila visual system

A conserved transcriptional network regulates lamina development in the Drosophila visual system

The sine oculis homeobox (SIX) family of transcription factors as regulators of development and disease

Confirmation of TFAP2A gene involvement in branchio‐oculo‐facial syndrome (BOFS) and report of temporal bone anomalies

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