<i>Sp8</i>controls the anteroposterior patterning at the midbrain-hindbrain border

Griesel, Gundula; Treichel, Dieter; Collombat, Patrick; Krull, Jens; Zembrzycki, Andreas; Akker, Willem M.R. van den; Gruß, Peter; Simeone, Antonio; Mansouri, Ahmed

doi:10.1242/dev.02326

Cited by 14 publications

(13 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 G and H). A posterior shift of gbx2 expression was observed, consistent with the previous study of sp8 as a midbrain-hindbrain boundary regulator (16). Although the ecl mutation did not show the severe head defects reported for the mouse, these expression analyses reveal that sp8 still has a conserved function to regulate brain development.…”

Section: Resultssupporting

confidence: 89%

See 1 more Smart Citation

Sp8 regulates inner ear development

Chung

Medina-Ruiz

Harland

2014

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

View full text Add to dashboard Cite

A forward genetic screen of N-ethyl-N-nitrosourea mutagenized Xenopus tropicalis has identified an inner ear mutant named eclipse (ecl). Mutants developed enlarged otic vesicles and various defects of otoconia development; they also showed abnormal circular and inverted swimming patterns. Positional cloning identified specificity protein 8 (sp8), which was previously found to regulate limb and brain development. Two different loss-of-function approaches using transcription activator-like effector nucleases and morpholino oligonucleotides confirmed that the ecl mutant phenotype is caused by down-regulation of sp8. Depletion of sp8 resulted in otic dysmorphogenesis, such as uncompartmentalized and enlarged otic vesicles, epithelial dilation with abnormal sensory end organs. When overexpressed, sp8 was sufficient to induce ectopic otic vesicles possessing sensory hair cells, neurofilament innervation in a thickened sensory epithelium, and otoconia, all of which are found in the endogenous otic vesicle. We propose that sp8 is an important factor for initiation and elaboration of inner ear development.T he vertebrate inner ear is a sensory organ responsible for balance and sound detection. Dysfunction of the inner ear is among the most common congenital disorders, affecting at least 1 in 500 births (1) and ∼40% of sensorineural deafness is associated with inner ear malformations (2). However, the study of hearing and balance impairment in humans is limited by the inability to follow inner ear development. Vertebrates share similarities in the sequence of developmental events that form the inner ear: the formation of an otic placode from an ectodermal thickening, morphogenesis to form the otocyst, and regional patterning of the otic vesicle (OV), resulting in the 3D membranous labyrinth (3, 4). Multipotent sensory progenitor cells are induced in the ectoderm surrounding the anterior neural plate, a domain termed the preplacodal region (PPR), and six1 has been characterized as marking this panplacodal domain. Signals from hindbrain and the regional expression of different transcription factors differentiate the PPR into the otic placode. The OV is partitioned by asymmetrical expression of various developmental regulators to pattern subdomains of the developing inner ear.The abilities of Xenopus to elucidate the cellular and molecular aspects of developmental processes position it as a valuable model organism (5-7). Earlier studies of lineage analysis and spatiotemporal expression of transcription factors during inner ear development led to construction of an inner ear fate map in Xenopus and this fate map allows us to interpret gene expression patterns within the context of the anatomy (8, 9). In recent years, genetic and genomic approaches have been developed in Xenopus tropicalis (10-13). To advance our understanding of inner ear development, we have screened N-ethyl-N-nitrosourea (ENU) mutagenized X. tropicalis colonies and recovered an inner ear mutant named eclipse (ecl). The ecl mutant perturbs specificity protei...

show abstract

Section: Resultssupporting

confidence: 89%

“…The zinc-finger transcription factor sp8 is related to Drosophila buttonhead. In mice, mutation of sp8 caused severe truncations of the limbs and tail and defective brain and abnormal olfactory development (14)(15)(16)(17). Limb/fin outgrowth in chick and zebrafish embryos also employs sp8 (18), suggesting the conserved function of sp8 across phylogeny.…”

mentioning

confidence: 99%

Sp8 regulates inner ear development

Chung

Medina-Ruiz

Harland

2014

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

View full text Add to dashboard Cite

show abstract

“…Sp8 is part of a transcriptional program that patterns neural progenitors into distinct domains (Griesel et al 2006;O'Leary et al 2007;Sahara et al 2007;Zembrzycki et al 2007;Kasberg et al 2013); however, a transcriptional network involving Sp8 during neural tube closure has not yet been identified. It will be interesting to determine whether there are shared targets of sptf-3 and Sp8.…”

Section: Discussionmentioning

confidence: 99%

Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure andCaenorhabditis elegansGastrulation

Sullivan-Brown

Tandon

et al. 2015

Genetics

View full text Add to dashboard Cite

Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways. We also identified members of the actin regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells' apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrate WAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems.

show abstract

“…6A). The physiological role of Sp8 in ameloblasts remains to be determined, although it has been reported that Sp8 is expressed during brain and limb bud development and demonstrated to regulate cortical patterning and limb outgrowth through FGF8 induction (26,27). In addition, gene expression of ameloblastin, one of the enamel-producing proteins, was significantly up-regulated in CHA9 cells compared with V1 cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

Sp6 downregulation of follistatin gene expression in ameloblasts

et al. 2008

View full text Add to dashboard Cite

: Sp6 is a member of the Sp family of transcription factors that regulate a wide range of cellular functions, such as cell growth and differentiation. Sp6, also called epiprofin, is specifically expressed in tooth germ, limb bud, and hair follicle, but there is little information on its function.To investigate the possible role of Sp6 in tooth development, first we established an Sp6-overproducing clone, CHA9, and analyzed the features of the cell, including cell proliferation and gene expression. The parental cells of CHA9 are the ameloblast-lineage G5 cells that we previously established from rat dental epithelia of lower incisor. Sp6 overproduction accelerated cell proliferation and induced the expression of ameloblastin mRNA, a marker of ameloblast differentiation. Second, we performed genome-wide screening of Sp6 target genes by microarray analysis. Out of a total 20,450 genes, 448 genes were up-regulated and 500 genes were down-regulated by Sp6. We found the expression of follistatin, a BMP antagonist, to be 22.4-fold lower in CHA9 than in control cells. Transfection of the Sp6-antisense construct into CHA9 cells restored follistatin expression back to equivalent levels seen in control cells, indicating that Sp6 regulates follistatin gene expression in ameloblasts.Our findings demonstrate that the follistatin gene is one of the Sp6 target genes in ameloblasts and suggest that Sp6 promotes amelogenesis through inhibition of follistatin gene expression. J. Med. Invest. 55 : 87-98, February, 2008

show abstract

Sp8controls the anteroposterior patterning at the midbrain-hindbrain border

Cited by 14 publications

References 41 publications

Sp8 regulates inner ear development

Sp8 regulates inner ear development

Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure andCaenorhabditis elegansGastrulation

Sp6 downregulation of follistatin gene expression in ameloblasts

Contact Info

Product

Resources

About