title: Esco2 regulates cx43 expression during skeletal regeneration in the zebrafish fin.
abstract: BACKGROUND
  Roberts syndrome (RBS) is a rare genetic disorder characterized by craniofacial abnormalities, limb malformation, and often severe mental retardation. RBS arises from mutations in ESCO2 that encodes an acetyltransferase and modifies the cohesin subunit SMC3. Mutations in SCC2/NIPBL (encodes a cohesin loader), SMC3 or other cohesin genes (SMC1, RAD21/MCD1) give rise to a related developmental malady termed Cornelia de Lange syndrome (CdLS). RBS and CdLS exhibit overlapping phenotypes, but RBS is thought to arise through mitotic failure and limited progenitor cell proliferation while CdLS arises through transcriptional dysregulation. Here, we use the zebrafish regenerating fin model to test the mechanism through which RBS-type phenotypes arise.
  
  
  RESULTS
  esco2 is up-regulated during fin regeneration and specifically within the blastema. esco2 knockdown adversely affects both tissue and bone growth in regenerating fins-consistent with a role in skeletal morphogenesis. esco2-knockdown significantly diminishes cx43/gja1 expression which encodes the gap junction connexin subunit required for cell-cell communication. cx43 mutations cause the short fin (sof(b123) ) phenotype in zebrafish and oculodentodigital dysplasia (ODDD) in humans. Importantly, miR-133-dependent cx43 overexpression rescues esco2-dependent growth defects.
  
  
  CONCLUSIONS
  These results conceptually link ODDD to cohesinopathies and provide evidence that ESCO2 may play a transcriptional role critical for human development.
authors.affiliation: Department of Biological Science, Lehigh University, Bethlehem, Pennsylvania.
authors.forename: Rajeswari
authors.initials: R
authors.lastname: Banerji
authors.affiliation: Department of Biological Science, Lehigh University, Bethlehem, Pennsylvania.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Eble
authors.affiliation: Department of Biological Science, Lehigh University, Bethlehem, Pennsylvania.
authors.forename: M Kathryn
authors.initials: MK
authors.lastname: Iovine
authors.affiliation: Department of Biological Science, Lehigh University, Bethlehem, Pennsylvania.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Skibbens
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D058500:Animal Fins / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001842:Bone and Bones / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D012038:Regeneration / Q000235:genetics*; D015854:Up-Regulation; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018031:Connexin 43; C561285:Esco2 protein, zebrafish; D029961:Zebrafish Proteins; D000123:Acetyltransferases
keywords: Roberts syndrome (RBS); cohesinopathy; cx43/gja1; esco2/ECO1/CTF7; gap junctions; oculodentodigital dysplasia (ODDD)