Showing papers by "Urban Lendahl published in 2017"

Notch Signaling in Development, Tissue Homeostasis, and Disease

Abstract: Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell com...

MIEF1/2 function as adaptors to recruit Drp1 to mitochondria and regulate the association of Drp1 with Mff

Abstract: Mitochondrial dynamics is a fundamental cellular process and recruitment of Drp1 to mitochondria is an essential step in mitochondrial fission. Mff and MIEF1/2 (MiD51/49) serve as key receptors for recruitment of Drp1 to mitochondria in mammals. However, if and how these receptors work together in mitochondrial fission is poorly understood. Here we show that MIEFs interact with both Drp1 and Mff on the mitochondrial surface and serve as adaptors linking Drp1 and Mff together in a trimeric Drp1-MIEF-Mff complex. Thus, MIEFs can regulate the interaction between Drp1 and Mff, and also Mff-induced Drp1 accumulation on mitochondria. It is shown that loss of endogenous MIEFs severely impairs these processes. Additionally, in cells depleted of endogenous MIEF1/2, high levels of exogenous MIEFs sequester Drp1 on the mitochondrial surface, resulting in mitochondrial elongation, whereas low-to-moderate levels of MIEFs promote mitochondrial fission, leading to mitochondrial fragmentation. In sum, the data suggest that MIEFs and Mff work coordinately in Drp1-mediated mitochondrial fission and that the level of MIEF1/2 relative to Mff sets the balance between mitochondrial fission and fusion.

An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis

Abstract: Craniofacial morphogenesis requires proper development of pharyngeal arches and epibranchial placodes. We show that the epibranchial placodes, in addition to giving rise to cranial sensory neurons, generate a novel lineage-related non-neuronal cell population for mouse pharyngeal arch development. Eya1 is essential for the development of epibranchial placodes and proximal pharyngeal arches. We identify an Eya1-Notch regulatory axis that specifies both the neuronal and non-neuronal commitment of the epibranchial placode, where Notch acts downstream of Eya1 and promotes the non-neuronal cell fate. Notch is regulated by the threonine phosphatase activity of Eya1. Eya1 dephosphorylates p-threonine-2122 of the Notch1 intracellular domain (Notch1 ICD), which increases the stability of Notch1 ICD and maintains Notch signaling activity in the non-neuronal epibranchial placodal cells. Our data unveil a more complex differentiation program in epibranchial placodes and an important role for the Eya1-Notch axis in craniofacial morphogenesis.

Lorenz Poellinger MD, PhD (1957-2016).

Abstract: Lorenz Poellinger suddenly passed away on March 13, 2016. He will be missed by his family, friends and colleagues around theworld. Lorenzwas an eminent scientist who providedmany important insights into the control of transcriptional regulation and how cells sense low oxygen (hypoxia). He was also a world traveler, mastered several languages and had a deep knowledge of history and culture. Lorenz graduated from the German Academy (Tyska Skolan) in Stockholm, Sweden, he was fluent in Swedish, English, German and French. Medicine became his next major interest and he obtained a PhD from the Karolinska Institute in 1985, with Professor Jan-Åke Gustafsson as his advisor, followed by an MD in 1991. In his doctoral work, he made important contributions to nuclear receptor biology. Following his PhD, Lorenz was a postdoctoral fellow with Professor Robert Roeder and again excelled in the area of gene regulation with a focus on the function of promoters and enhancers. After his return to Sweden in the late 1980s Lorenz continued to explore the mechanisms of gene regulation, and his work on the PAS domain in the dioxin receptor and its interaction with ARNT (HIF1β) led him into a new research field, the cellular hypoxic response, where he would become a true international leader. As a measure of his success he received prestigious awards, like the Anders Jahre Prize for Young Medical Investigators in 1995 and the The Svedberg Prize in 1996. He was appointed Professor of Molecular Biology at the Karolinska Institute at the young age of 39, in 1996. Lorenz’ work in the field of cellular hypoxia was broad and multifaceted, and he provided numerous important insights into how cells and organisms cope with low oxygen levels. Among his discoverieswas themechanism for how the cornea remains avascular based on the function of IPAS (a hypoxiainducible splicing variant of HIF3α). I had the honor and privilege to work with Lorenz on unraveling a cross-talk between the cellular hypoxic response and Notch signaling, and this project would have gone nowhere without Lorenz’ deep expertise, enthusiasm and scientific generosity. Lorenz was a leading scientist at the Karolinska Institute. He was awarded the Distinguished Professor Award in 2010 and since 2007 he was a member of the Nobel Assembly for Physiology or Medicine, where he was an important voice with his broad knowledge in biochemistry, molecular biology and physiology. In 2008 Lorenz took the next step in his career, by establishing a satellite laboratory for tumor and hypoxia biology at the Cancer Science Institute of Singapore, a city that became very close to his and his wife Eva’s hearts. Lorenz was truly multi-talented. In addition to being a firstrate scientist, he had a 'joie de vivre' attitude to life. He was a keen mountain climber in his youth and he liked good food, traveling and culture; a coffee room discussion with Lorenz could equally well end up on the role of a specific amino acid in HIF1 as in stories on European history or memories from traveling to remote parts of the world. But above all, Lorenz was truly passionate about science; with an insatiable curiosity for how the cell works at the molecular level. I will always remember our last conversation; he came to my office to share his excitement over a new aspect of hypoxia, S-2hydroxyglutarate, and how this affects cells in the immune system; a paper that was just recently published in Nature. Lorenz will be missed by many friends and colleagues in Sweden and abroad. I thank Katarina Gradin for biographical information.