The Chromatin Modifier MSK1/2 Suppresses Endocrine Cell Fates during Mouse Pancreatic Development

Type I diabetes is caused by loss of insulin-secreting beta cells. To identify novel, pharmacologically-targetable histone-modifying proteins that enhance beta cell production from pancreatic progenitors, we performed a screen for histone modifications induced by signal transduction pathways at key pancreatic genes. The screen led us to investigate the temporal dynamics of ser-28 phosphorylated histone H3 (H3S28ph) and its upstream kinases, MSK1 and MSK2 (MSK1/2). H3S28ph and MSK1/2 were enriched at the key endocrine and acinar promoters in E12.5 multipotent pancreatic progenitors. Pharmacological inhibition of MSK1/2 in embryonic pancreatic explants promoted the specification of endocrine fates, including the beta-cell lineage, while depleting acinar fates. Germline knockout of both Msk isoforms caused enhancement of alpha cells and a reduction in acinar differentiation, while monoallelic loss of Msk1 promoted beta cell mass. Our screen of chromatin state dynamics can be applied to other developmental contexts to reveal new pathways and approaches to modulate cell fates

A new dinosaur (Theropoda, Spinosauridae) from the Cretaceous (Cenomanian) Alcântara Formation, Cajual Island, Brazil

A new spinosaurid taxon, Oxalaia quilombensis gen. et sp. nov., is described based on the anterior part of a snout and a fragment of a maxilla. These specimens were collected at the Laje do Coringa site, Late Cretaceous (Cenomanian) of the São Luis Basin. Unlike Cristatusaurus and Suchomimus, Oxalaia quilombensis lacks serrations on the teeth. The new species differs from Angaturama limai by having the anterior part of the premaxillae more expanded and by lacking a sagittal premaxillary crest. It further differs from Spinosaurus cf. S. aegyptiacus and the Algerian spinosaurid by the rounder shape of the terminal expansion. Furthermore, xalaia quilobensis has one functional tooth followed by two replacement teeth, a feature not previously observed in theropods. Oxalaia quilombensis appears to be more closely related to the spinosaurids found in North Africa than to the Brazilian members of this clade and thus further increases the diversity of these enigmatic predatory dinosaurs in this country