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Ligament versus bone cell identity in the zebrafish hyoid skeleton is regulated by mef2ca.

Publication ,  Journal Article
Nichols, JT; Blanco-Sánchez, B; Brooks, EP; Parthasarathy, R; Dowd, J; Subramanian, A; Nachtrab, G; Poss, KD; Schilling, TF; Kimmel, CB
Published in: Development
December 1, 2016

Heightened phenotypic variation among mutant animals is a well-known, but poorly understood phenomenon. One hypothetical mechanism accounting for mutant phenotypic variation is progenitor cells variably choosing between two alternative fates during development. Zebrafish mef2cab1086 mutants develop tremendously variable ectopic bone in their hyoid craniofacial skeleton. Here, we report evidence that a key component of this phenotype is variable fate switching from ligament to bone. We discover that a 'track' of tissue prone to become bone cells is a previously undescribed ligament. Fate-switch variability is heritable, and comparing mutant strains selectively bred to high and low penetrance revealed differential mef2ca mutant transcript expression between high and low penetrance strains. Consistent with this, experimental manipulation of mef2ca mutant transcripts modifies the penetrance of the fate switch. Furthermore, we discovered a transposable element that resides immediately upstream of the mef2ca locus and is differentially DNA methylated in the two strains, correlating with differential mef2ca expression. We propose that variable transposon epigenetic silencing underlies the variable mef2ca mutant bone phenotype, and could be a widespread mechanism of phenotypic variability in animals.

Duke Scholars

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Published In

Development

DOI

EISSN

1477-9129

Publication Date

December 1, 2016

Volume

143

Issue

23

Start / End Page

4430 / 4440

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Stem Cells
  • Skull
  • Penetrance
  • Osteogenesis
  • Osteoblasts
  • MEF2 Transcription Factors
  • Ligaments
  • Hyoid Bone
 

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Nichols, J. T., Blanco-Sánchez, B., Brooks, E. P., Parthasarathy, R., Dowd, J., Subramanian, A., … Kimmel, C. B. (2016). Ligament versus bone cell identity in the zebrafish hyoid skeleton is regulated by mef2ca. Development, 143(23), 4430–4440. https://doi.org/10.1242/dev.141036
Nichols, James T., Bernardo Blanco-Sánchez, Elliott P. Brooks, Raghuveer Parthasarathy, John Dowd, Arul Subramanian, Gregory Nachtrab, Kenneth D. Poss, Thomas F. Schilling, and Charles B. Kimmel. “Ligament versus bone cell identity in the zebrafish hyoid skeleton is regulated by mef2ca.Development 143, no. 23 (December 1, 2016): 4430–40. https://doi.org/10.1242/dev.141036.
Nichols JT, Blanco-Sánchez B, Brooks EP, Parthasarathy R, Dowd J, Subramanian A, et al. Ligament versus bone cell identity in the zebrafish hyoid skeleton is regulated by mef2ca. Development. 2016 Dec 1;143(23):4430–40.
Nichols, James T., et al. “Ligament versus bone cell identity in the zebrafish hyoid skeleton is regulated by mef2ca.Development, vol. 143, no. 23, Dec. 2016, pp. 4430–40. Pubmed, doi:10.1242/dev.141036.
Nichols JT, Blanco-Sánchez B, Brooks EP, Parthasarathy R, Dowd J, Subramanian A, Nachtrab G, Poss KD, Schilling TF, Kimmel CB. Ligament versus bone cell identity in the zebrafish hyoid skeleton is regulated by mef2ca. Development. 2016 Dec 1;143(23):4430–4440.
Journal cover image

Published In

Development

DOI

EISSN

1477-9129

Publication Date

December 1, 2016

Volume

143

Issue

23

Start / End Page

4430 / 4440

Location

England

Related Subject Headings

  • Zebrafish Proteins
  • Zebrafish
  • Stem Cells
  • Skull
  • Penetrance
  • Osteogenesis
  • Osteoblasts
  • MEF2 Transcription Factors
  • Ligaments
  • Hyoid Bone