Evx1 is required for joint formation in zebrafish fin dermoskeleton

Schulte, Claus J.; Allen, Claire; England, Samantha J.; Juárez-Morales, José L.; Lewis, Katharine E.

doi:10.1002/dvdy.22534

Cited by 41 publications

(54 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The evx1 i232 , evx2 sa140 and lmx1bb jj410 mutants have been previously described [11, 37–39] . All three of these mutations are single base pair changes that lead to premature stop codons before the homeobox.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

et al. 2016

Self Cite

View full text Add to dashboard Cite

BackgroundAlterations in neurotransmitter phenotypes of specific neurons can cause imbalances in excitation and inhibition in the central nervous system (CNS), leading to diseases. Therefore, the correct specification and maintenance of neurotransmitter phenotypes is vital. As with other neuronal properties, neurotransmitter phenotypes are often specified and maintained by particular transcription factors. However, the specific molecular mechanisms and transcription factors that regulate neurotransmitter phenotypes remain largely unknown.MethodsIn this paper we use single mutant, double mutant and transgenic zebrafish embryos to elucidate the functions of Lmx1ba and Lmx1bb in the regulation of spinal cord interneuron neurotransmitter phenotypes.ResultsWe demonstrate that lmx1ba and lmx1bb are both expressed in zebrafish spinal cord and that lmx1bb is expressed by both V0v cells and dI5 cells. Our functional analyses demonstrate that these transcription factors are not required for neurotransmitter fate specification at early stages of development, but that in embryos with at least two lmx1ba and/or lmx1bb mutant alleles there is a reduced number of excitatory (glutamatergic) spinal interneurons at later stages of development. In contrast, there is no change in the numbers of V0v or dI5 cells. These data suggest that lmx1b-expressing spinal neurons still form normally, but at least a subset of them lose, or do not form, their normal excitatory fates. As the reduction in glutamatergic cells is only seen at later stages of development, Lmx1b is probably required either for the maintenance of glutamatergic fates or to specify glutamatergic phenotypes of a subset of later forming neurons. Using double labeling experiments, we also show that at least some of the cells that lose their normal glutamatergic phenotype are V0v cells. Finally, we also establish that Evx1 and Evx2, two transcription factors that are required for V0v cells to acquire their excitatory neurotransmitter phenotype, are also required for lmx1ba and lmx1bb expression in these cells, suggesting that Lmx1ba and Lmx1bb act downstream of Evx1 and Evx2 in V0v cells.ConclusionsLmx1ba and Lmx1bb function at least partially redundantly in the spinal cord and three functional lmx1b alleles are required in zebrafish for correct numbers of excitatory spinal interneurons at later developmental stages. Taken together, our data significantly enhance our understanding of how spinal cord neurotransmitter fates are regulated.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Fin biopsy and evx1 and evx2 genotyping of adults were performed as previously described [11, 37]. KASP assays, designed by LGC Genomics LLC, using DNA extracted from head dissections, were used to identify embryos carrying the evx1 i232 and evx2 sa140 mutations.…”

Section: Methodsmentioning

confidence: 99%

Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…In lepidotrichia (bony ray), Evx1 is required for joint formation in the fin dermoskeleton, while endoskeletal joints require Gdf5 instead. In the light of the well-established importance of Gdf5 for joint formation, this alternative pathway in lepidotrichia dermoskeletal fin joints invites further studies in mammalian species [46].…”

Section: Discussionmentioning

confidence: 99%

Differential Gene Expression of the Intermediate and Outer Interzone Layers of Developing Articular Cartilage in Murine Embryos

Jenner

IJpma

Cleary

et al. 2014

Stem Cells and Development

View full text Add to dashboard Cite

Nascent embryonic joints, interzones, contain a distinct cohort of progenitor cells responsible for the formation of the majority of articular tissues. However, to date the interzone has largely been studied using in situ analysis for candidate genes in the context of the embryo rather than using an unbiased genome-wide expression analysis on isolated interzone cells, leaving significant controversy regarding the exact role of the intermediate and outer interzone layers in joint formation. Therefore, in this study, using laser capture microdissection (three biological replicates), we selectively harvested the intermediate and outer interzones of mouse embryos at gestational age 15.5 days, just prior to cavitation, when the differences between the layers should be most profound. Microarray analysis (Agilent Whole Mouse Genome Oligo Microarrays) was performed and the differential gene expression between the intermediate interzone cells and outer interzone cells was examined by performing a two-sided paired Student's t-test and pathway analysis. One hundred ninety-seven genes were differentially expressed ( ‡ 2-fold) between the intermediate interzone and the outer interzone with a P-value £ 0.01. Of these, 91 genes showed higher expression levels in the intermediate interzone and 106 were expressed higher in the outer interzone. Pathway analysis of differentially expressed genes suggests an important role for inflammatory processes in the interzone layers, especially in the intermediate interzone, and hence in joint and articular cartilage development. The high representation of genes relevant to chondrocyte hypertrophy and endochondral ossification in the outer interzone suggests that it undergoes endochondral ossification.

show abstract

“…The phenotypes of lof and evx1 mutants suggest that joint patterning and fin growth may be regulated independently (Iovine and Johnson, 2000;Schulte et al, 2011). Therefore, it is reasonable to assume the presence of a morphogen specifically involved in joint formation.…”

Section: Model 2: Model Of Ray Joint Pattern Formation During Fin Devmentioning

confidence: 99%

“…The fact that fin length and segment length are both altered in sof and alf mutants suggests that mechanisms controlling fin growth and joint formation are closely related (Sims et al, 2009). However, the long fin (lof) mutant has long fins but only slightly longer segments than wild type (Iovine and Johnson, 2000), and the evx1 mutant, which lacks joints, has an apparently normal fin length (Schulte et al, 2011). Those two latter phenotypes provide evidence that ray growth and joint formation may be uncoupled.…”

Section: Introductionmentioning

confidence: 99%

Morphogen-based simulation model of ray growth and joint patterning during fin development and regeneration

et al. 2012

View full text Add to dashboard Cite

SUMMARYThe fact that some organisms are able to regenerate organs of the correct shape and size following amputation is particularly fascinating, but the mechanism by which this occurs remains poorly understood. The zebrafish (Danio rerio) caudal fin has emerged as a model system for the study of bone development and regeneration. The fin comprises 16 to 18 bony rays, each containing multiple joints along its proximodistal axis that give rise to segments. Experimental observations on fin ray growth, regeneration and joint formation have been described, but no unified theory has yet been put forward to explain how growth and joint patterns are controlled. We present a model for the control of fin ray growth during development and regeneration, integrated with a model for joint pattern formation, which is in agreement with published, as well as new, experimental data. We propose that fin ray growth and joint patterning are coordinated through the interaction of three morphogens. When the model is extended to incorporate multiple rays across the fin, it also accounts for how the caudal fin acquires its shape during development, and regains its correct size and shape following amputation.

show abstract

Evx1 is required for joint formation in zebrafish fin dermoskeleton

Cited by 41 publications

References 26 publications

Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons

Differential Gene Expression of the Intermediate and Outer Interzone Layers of Developing Articular Cartilage in Murine Embryos

Morphogen-based simulation model of ray growth and joint patterning during fin development and regeneration

Contact Info

Product

Resources

About