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Research news

July 12, 2016

Hairs, feathers and scales have a lot in common

Skin placodes in crocodile (left), lizard (middle) and snake (right) Nicolas Di-Poi

Skin placodes in crocodile (left), lizard (middle) and snake (right).

 

Dr Nicolas Di-Poï and Professor Michel C. Milinkovitch demonstrate that hairs in mammals, feathers in birds and scales in reptiles share a common ancestry. On the basis of new analyses of embryonic development, the Finnish and Swiss biologists evidenced molecular and micro-anatomical signatures that are identical between hairs, feathers, and scales at their early developmental stages. These new observations indicate that the three structures evolved from their common reptilian ancestor.

Mammalian hairs and avian feathers develop from a similar primordial structure called a 'placode': a local thickening of the epidermis with columnar cells that reduce their rate of proliferation and express very specific genes.

This observation has puzzled evolutionary and developmental biologists for many years because birds and mammals are not sister groups: they evolved from different reptilian lineages. According to previous studies, reptiles' scales however do not develop from an anatomical placode. This would imply that birds and mammals have independently 'invented' placodes during their evolution.

Michel C. Milinkovitch and Nicolas Di-Poï, group leader at the Institute of Biotechnology put this long controversy to rest by demonstrating that scales in reptiles develop from a placode with all the anatomical and molecular signatures of avian and mammalian placodes.

This indicates that the three types of skin appendages are homologous: the reptilian scales, the avian feathers and the mammalian hairs, despite their very different final shapes, evolved from the scales of their reptilian common ancestor.

During their new study, the researchers also investigated a mutant form of the bearded dragon lizard that lacks all scales. By analyzing the genome of this mutant, Di-Poï et Milinkovitch have discovered that the peculiar look of these naked lizards is due to the disruption of the ectodysplasin-A (EDA), a gene whose mutations in humans and mice are known to generate substantial abnormalities in the development of teeth, glands, nails and hairs.

The researchers have demonstrated that, when EDA is malfunctioning in lizards, they fail to develop a proper scale placode, exactly as mammals or birds affected with similar mutations in that same gene cannot develop proper hairs or feathers placodes. These data all coherently indicate the common ancestry between scales, feathers and hairs.

Article
Picture: Nicolas Di-Poï

June 1, 2016

Professor Pekka Lappalainen is a new member of EMBO

EMBO has newly elected 58 researchers in the life sciences to its membership. New members are elected annually in recognition of their contributions to scientific excellence.

50 of the now elected scientists reside in 13 different countries in Europe. Eight Associate Members were elected from China, Japan, Lithuania, Singapore and the United States.

Professor, research director Pekka Lappalainen is the only Finnish researcher elected as EMBO member in 2016. The research in the laboratory of Pekka Lappalainen is focused on understanding the mechanisms that control the organization and dynamics of the actin cytoskeleton in animal cells.

“Because defects in regulation of the actin cytoskeleton are associated to many diseases such as cancer progression as well as neurological and immunological disorders, these studies are also expected to elucidate the molecular basis of these diseases,” Pekka Lappalainen says.

Pekka Lappalainen did his PhD-thesis work at EMBL-Heidelberg, Germany, on structural biology and biochemistry of cytochrome oxidase. This was followed by a 3-year post-doctoral period at University of California, Berkeley, USA, where he began to study the actin cytoskeleton.

Since 1998, Pekka Lappalainen has worked as a group leader at Institute of Biotechnology.

More than 1700 members around the world

EMBO Members and Associate Members are more than 1700 of the best researchers in Europe and around the world. Ordinary members reside or were elected while residing in an EMBC Member State, and associate members reside outside of the EMBC Member States.

Election to EMBO Membership is recognition of research excellence and the outstanding achievements made by a life scientist. 84 EMBO Members and Associate Members have been awarded Nobel Prizes. The annual nominations and elections ensure that the membership remains at the forefront of life science research.

“I am delighted by the addition of 58 outstanding scientists to our membership. I would like to congratulate them and welcome them to the EMBO community”, EMBO Director Maria Leptin stated. “By serving the principles of excellence and integrity through their views and actions, they make invaluable contributions to science and society.”  

New EMBO members and associate members 2016

Text and picture: Elina Raukko

May 10, 2016

A novel regulator of hair follicle stem cell specification identified

Adult tissue-specific stem cells are intensively studied, but how they are established during development is poorly understood. Knowledge of stem cell origins forms the foundation of understanding tissue homeostasis, dissecting mechanisms underlying diseases displaying aberrant stem cell behavior such as cancer, and developing tools for regenerative biology. The hair follicle offers an ideal system to study stem cell specification and maintenance due to its well characterized morphogenesis and stereotypic cycles of stem cell activation upon each hair cycle to produce a new hair shaft.

In a study recently published in Stem Cells, Vera Shirokova, a PhD student in Marja Mikkola’s lab, and her coworkers focused their attention on transcription factor Foxi3. Previous studies had revealed that hairlessness of three dog breeds (Peruvian hairless, Mexican hairless, and Chinese crested) is due to a heterozygous mutation in Foxi3 but the underlying causes had remained unknown. The new study took advantage of a Foxi3 deficient mouse model generated in Andrew Groves’ lab (Baylor College of Medicine, Houston). It revealed that lack of Foxi3 impairs hair follicle growth from the earliest developmental stage onwards. Importantly, it identified a critical role for Foxi3 in hair follicle stem cell specification. In the absence of Foxi3, stem cells are established but many critical stem cell regulators are expressed at reduced levels. Consequently, hair follicle renewal is severely compromised. The results also suggested that critical stem cell fate decisions take place earlier than previously recognized, prior to the appearance of a morphologically discernible stem cell niche.

Shirokova V, Biggs LC, Jussila M, Ohyama T, Groves AK, Mikkola ML. Foxi3 deficiency compromises hair follicle stem cell specification and activation. Stem Cells. doi: 10.1002/stem.2363.

Stem cell marker Nfatc1 (red) was not detected in the prospective hair follicle stem cell population in 18 day old Foxi3 null embryos.

Article in PubMed

Picture: Mikkola group

March 30, 2016

Pekka Lappalainen receives prestigious Human Frontier Science Program grant

Research director Pekka Lappalainen at the Institute of Biotechnology and his colleagues from France and USA have been awarded a three-year grant worth over one million USD to research filopodia formation mechanism. A joint project of the research director Pekka Lappalainen at the Institute of Biotechnology, Professor Patricia Bassereau at Curie Institute, France, and Professor Gregory Voth at the University of Chicago, USA, has been awarded a Human Frontier Science Program Research Grant to investigate the filopodia formation mechanism by physical, computational and biological approaches. Bassereau, Lappalainen and Voth will share 1,050,000 USD for the three-year project.

Filopodia are thin, actin-rich protrusions at the cell edge. They function as "antennae" that the cells use to probe their microenvironment during cell migration. They are also involved in guidance towards chemoattractants, neuronal pathfinding, synapse formation, and embryonic development.

- Defects in formation or dynamics of filopodia are linked to many diseases such as cancer cell invasion and neurological disorders. The mechanisms by which the filopodia are generated in cells are still largely unknown. We intend to find them out. My group is going to be responsible for the cell biological work. The Basserau lab concentrates on biophysical methods, and the Voth lab on computational methods, Pekka Lappalainen describes.

The groups have a specific interest to reveal how various filopodial proteins communicate with the plasma membrane during these processes. Collectively, they hope to uncover new general principles behind the formation of membrane protrusions in cells, and additionally elucidate the principles of various human disorders associated with abnormal filopodia dynamics.

The International Human Frontier Science Program Organization (HFSPO) awarded about 34 million USD to the 32 winning teams of the 2016 competition for the HFSP Research Grants.

Human osteosarcoma cells exhibiting thin filopodial protrusions.

Picture: Yosuke Senju

March 9, 2016

Mouse teeth help us refine humanity’s family tree

Mouse studies conducted at the University of Helsinki have generated a significant tool for studying the beginnings of the humans.

An international group of researchers has developed a model enabling them to predict the size of teeth in a tooth row based on a single tooth. This model is a quantitative tool for paleoanthropologists who are piecing together the evolutionary path of humans, often from isolated fossil teeth.

The new study has revealed that tooth size in human ancestors that lived before 2.5 million years ago tended to follow one pattern, while members of our own group, Homo, tended to follow another pattern. The seed for the loss of the wisdom teeth in modern humans appears to have been laid down at the onset of Homo, when tooth size and proportions got mechanistically coupled.

The model can also be used to address taxonomic controversies. For example, Homo habilis, commonly thought to be the earliest member of the Homo genus, may, in fact, fit better the genus Australopithecus based on its teeth.

Based on research from the University of Helsinki

The model now published in Nature stems from a study published eight years ago on the development of mouse teeth, conducted at the University of Helsinki's Institute of Biotechnology under Academy professor Jukka Jernvall. The study showed experimentally that that tooth size in the mouse is determined by combination of factors inhibiting and activating tooth development. A mathematical extension of the inhibitory cascade provides a developmental baseline or rule that predicts how tooth size and proportions should evolve, with a limited number of evolutionary outcomes. The first author of the new article, Alistair Evans, worked in Jernvall’s group for several years.

“Even though the original study on rodents comes from Helsinki, human evolution is not our specialty. This is why we needed international cooperation. Next we intend to determine the genetic bases of the model by studying teeth that are sufficiently simple, namely, the teeth of the Saimaa ringed seal" says Jukka Jernvall, who leads the Academy of Finland’s Centre of Excellence in Experimental and Computational Developmental Biology.

Evans AR, Daly ES, Catlett KK, Paul KS, King SJ, Skinner MM, Nesse HP, Hublin JJ, Townsend GC, Schwartz GT, Jernvall J. A simple rule governs the evolution and development of hominin tooth size. Nature. 2016 Feb 25;530(7591):477-80.

Article in Nature

February 8, 2016

Boosting the body’s own production of neurothrophic factors could help Parkinson’s sufferers

A recent study indicates that GDNF clearly regulates the function of the dopaminergic neurons in the midbrain. With the help of a new research method, the amount of GDNF was topically increased specifically in the areas of the brain associated with GDNF production, such as the areas which are central to the development of Parkinson's disease.

The motor symptoms of Parkinson’s result from the gradual loss of function and subsequent destruction of dopaminergic neurons in the midbrain. GDNF-based therapy has been one of the most promising treatments for Parkinson’s. In animal models, GDNF injected directly into the head has effectively protected dopaminergic neurons from experimental damage, and even repaired existing damage.

The efficacy of GDNF has also been tested on Parkinson’s sufferers, but despite initial promising results, extensive benefit was not conclusively established in the two second-stage clinical studies so far conducted.

“The modest results are likely at least partially attributable to problems with dosage and delivery. GDNF is a large protein, so introducing it directly into brain tissue is difficult, and can result in uncontrolled neurite outgrowth at the injection site.  Further information is also needed on the mechanisms through which GDNF influences the dopaminergic neurons, particularly in the ageing brain,” states Jaan-Olle Andressoo, principal investigator at the University of Helsinki’s Institute of Biotechnology.

Controlled release of GDNF possible

Jaan-Olle Andressoo has developed a new microRNA-based method for increasing the amount of GDNF in the brain.
“The benefit of the resulting mouse model is that the amount of GDNF is increased in a controlled manner and only in the cells that normally express it. In the part of the brain most crucial for Parkinson's disease, the striatum, the expression of GDNF was doubled. In addition, the expression remains susceptible to normal gene regulation. This means we can gain information on the physiological effects of GDNF, which was not possible with previous methods,” Jaan-Olle Andressoo explains.

In follow-up studies conducted at the University of Helsinki's Faculty of Pharmacy, the overexpression of GDNF was found to slightly increase the number of dopaminergic neurons as well as the amount of dopamine in the striatum. The overexpression also enhanced the release of dopamine and protected the neurons from damage.

The impact on Parkinson’s disease was studied together with Professor Mart Saarma. Researchers from Umeå University and the University of Tartu also participated in studying GDNF’s mechanisms of action.

Based on the research results, principal investigator Jaan-Olle Andressoo is now developing methods which would enable the increase bodies own GDNF levels inside the brain.

“If we succeed, we will probably be able to restore neural connections that have already been weakened using specific elevation of bodies own neurotrophic factors, first among Parkinson’s sufferers, and later among patients with other degenerative neural illnesses. Our preliminary results are highly promising,” suggests Andressoo.

Kumar A, Kopra J, Varendi K, Porokuokka LL, Panhelainen A, Kuure S, Marshall P, Karalija N, Härma MA, Vilenius C, Lilleväli K, Tekko T, Mijatovic J, Pulkkinen N, Jakobson M, Jakobson M, Ola R, Palm E, Lindahl M, Strömberg I, Võikar V, Piepponen TP, Saarma M, Andressoo JO. GDNF Overexpression from the Native Locus Reveals its Role in the Nigrostriatal Dopaminergic System Function. PLoS Genet. 2015;11(12):e1005710

Article in Plos Genetics

February 3, 2016

A new open access software for processing and quantification microscopy datasets

Multidimensional light (LM) and electron (EM) microscopy imaging is among the key methods in biosciences nowadays. The knowledge of complex 3-D structures of cells and cell organelles in their natural context is important for understanding the structure-function relationship. As the amount of collected data is exponentially increasing, the effectiveness of processing raw data into analyzed results has key importance. 

To address the challenges of processing of large microscopy datasets, over the last four years the research team of Eija Jokitalo at the Electron Microscopy Unit of the Institute of Biotechnology, has been developing their own software solution: Microscopy Image Browser (MIB). MIB is an open source software aimed for efficient processing and image segmentation of multidimensional datasets obtained by both LM and EM. Use of MIB improves and eases the full utilization of the acquired data and allows quantitatively analyze morphological features. The effectiveness of using MIB in research has been already proved in more than 10 different scientific projects, ranging from cellular level to whole organisms. MIB is a flexible package that is easily extended with a custom plugins to address specific questions of any research project.

Concomitant to publishing a paper describing its features, MIB was officially released under the terms of the GNU General Public License v2 and is now freely available from a dedicated website: http://mib.helsinki.fi. In addition to the program itself, the website contains a collection of test cases and video tutorials.  

Belevich I, Joensuu M, Kumar D, Vihinen H, Jokitalo E. (2015) Microscopy Image Browser: A Platform for Segmentation and Analysis of Multidimensional Datasets. PLoS Biol.14(1):e1002340.

A collage image of a graphical user interface of Microscopy Image Browser (MIB) and a 3D model of Trypanosoma brucei. The dataset was obtained with Serial Block Face Scanning Electron Microscopy and processed and segmented using MIB. Image by Ilya Belevich, Institute of Biotechnology, University of Helsinki.


Article in PLoS Biology.
Picture: EM unit

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