title: Ligament versus bone cell identity in the zebrafish hyoid skeleton is regulated by mef2ca.
abstract: 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 mef2cab1086mutants 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.
authors: Department of Biology, University of Oregon, Eugene, OR 97403, USA james.nichols@ucdenver.edu.
authors: James T
authors: 0000-0002-7263-1704
authors: JT
authors: Nichols
authors: Department of Biology, University of Oregon, Eugene, OR 97403, USA.
authors: Bernardo
authors: B
authors: Blanco-Sánchez
authors: Department of Biology, University of Oregon, Eugene, OR 97403, USA.
authors: Elliott P
authors: EP
authors: Brooks
authors: Department of Physics, University of Oregon, Eugene, OR 97403, USA.
authors: Raghuveer
authors: R
authors: Parthasarathy
authors: Department of Biology, University of Oregon, Eugene, OR 97403, USA.
authors: John
authors: J
authors: Dowd
authors: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.
authors: Arul
authors: A
authors: Subramanian
authors: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Gregory
authors: G
authors: Nachtrab
authors: Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Kenneth D
authors: KD
authors: Poss
authors: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA.
authors: Thomas F
authors: TF
authors: Schilling
authors: Department of Biology, University of Oregon, Eugene, OR 97403, USA.
authors: Charles B
authors: CB
authors: Kimmel
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019175:DNA Methylation / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006928:Hyoid Bone / Q000254:growth & development*; D008022:Ligaments / Q000254:growth & development*; D064326:MEF2 Transcription Factors / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000502:physiology*; D019683:Penetrance; D012886:Skull / Q000254:growth & development*; D013234:Stem Cells / Q000166:cytology*; D015027:Zebrafish / Q000196:embryology* / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D004251:DNA Transposable Elements; D064326:MEF2 Transcription Factors; C588168:Mef2ca protein, zebrafish; D029961:Zebrafish Proteins
keywords: Bone; Craniofacial skeleton; Ligament; Variability; Zebrafish; mef2ca