Genomic profiling of Mixer and Sox17β targets during <i>Xenopus</i> endoderm development

Dickinson, Kari; Leonard, Jeffrey M.; Baker, Julie C.

doi:10.1002/dvdy.20636

Cited by 17 publications

(15 citation statements)

References 60 publications

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“…Among these genes, sp8 is transiently expressed in the OV in mouse embryos (15) so we analyzed expression patterns of sp8 in X. tropicalis by in situ hybridization in WT and mutant embryos. As also reported for EST10 (19), staining for sp8 mRNA was found in the olfactory bulb, midbrain, hindbrain, and the OV in WT embryos, whereas no such signals were detected in ecl mutants ( Fig. 1 E-H).…”

Section: Resultssupporting

confidence: 83%

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Sp8 regulates inner ear development

Chung

Medina-Ruiz

Harland

2014

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

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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...

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Section: Resultssupporting

confidence: 83%

“…Limb/fin outgrowth in chick and zebrafish embryos also employs sp8 (18), suggesting the conserved function of sp8 across phylogeny. In Xenopus, the gene was identified as a target of sox17 (19). Here, we demonstrate a role for sp8 in inner ear development.…”

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confidence: 60%

Sp8 regulates inner ear development

Chung

Medina-Ruiz

Harland

2014

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

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“…1H,O). There may also be a difference in regulation between endodermal transcripts, which reflects the intricate network of gene regulation involved in endoderm formation reported in array experiments (Dickinson et al, 2006;Sinner et al, 2006).…”

Section: The Effects Of Fgf Signal Inhibition On Early Endodermal Andmentioning

confidence: 99%

The role of FGF signaling in the establishment and maintenance of mesodermal gene expression in Xenopus

Fletcher

Harland

2008

Developmental Dynamics

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FGF signaling is important for the formation of mesoderm in vertebrates, and when it is perturbed in Xenopus, most trunk and tail mesoderm fails to form. Here we have further dissected the activities of FGF in patterning the embryo by addressing its inductive and maintenance roles. We show that FGF signaling is necessary for the establishment of xbra expression in addition to its well-characterized role in maintaining xbra expression. The role of FGF signaling in organizer formation is not clear in Xenopus. We find that FGF signaling is essential for the initial specification of paraxial mesoderm but not for activation of several pan-mesodermal and most organizer genes; however, early FGF signaling is necessary for the maintenance of organizer gene expression into the neurula stage. Inhibition of FGF signaling prevents VegT activation of specific mesodermal transcripts. These findings illuminate how FGF signaling contributes to the establishment of distinct types of mesoderm.

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“…Over the past few years extensive investigation has contributed to the elucidation of the molecular mechanisms underlying initial endoderm formation (Dickinson et al, 2006;Ober et al, 2003;Sinner et al, 2006;Tam et al, 2003;Taverner et al, 2005). However, we still know relatively little about subsequent endodermal patterning and how different domains of the endoderm progressively become specialized to generate distinct organ primordia.…”

Section: Introductionmentioning

confidence: 99%

TheGata5target,TGIF2, defines the pancreatic region by modulating BMP signals within the endoderm

Spagnoli

Brivanlou

2008

Development

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Mechanisms underlying regional specification of distinct organ precursors within the endoderm, including the liver and pancreas, are still poorly understood. This is particularly true for stages between endoderm formation and the initiation of organogenesis. In this report, we have investigated these intermediate steps downstream of the early endodermal factor Gata5, which progressively lead to the induction of pancreatic fate. We have identified TGIF2 as a novel Gata5 target and demonstrate its function in the establishment of the pancreatic region within dorsal endoderm in Xenopus. TGIF2 acts primarily by restricting BMP signaling in the endoderm to allow pancreatic formation. Consistently, we found that blocking BMP signaling by independent means also perturbs the establishment of pancreatic identity in the endoderm. Previous findings demonstrated a crucial role for BMP signaling in determining dorsal/ventral fates in ectoderm and mesoderm. Our results now extend this trend to the endoderm and identify TGIF2 as the molecular link between dorsoventral patterning of the endoderm and pancreatic specification.

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Genomic profiling of Mixer and Sox17β targets during Xenopus endoderm development

Cited by 17 publications

References 60 publications

Sp8 regulates inner ear development

Sp8 regulates inner ear development

The role of FGF signaling in the establishment and maintenance of mesodermal gene expression in Xenopus

TheGata5target,TGIF2, defines the pancreatic region by modulating BMP signals within the endoderm

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