Developmental Biology

a worm

News Blog

Publication in Science Advances

Aniek

SWI/SNF (switch/sucrose nonfermenting) complexes regulate transcription through chromatin remodeling and opposing gene silencing by Polycomb group (PcG) proteins. Genes encoding SWI/SNF components are critical for normal development and frequently mutated in human cancer. Our former postdocs van der Vaart and Godfrey and current postdoc Vincent Portegijs characterized the in vivo contributions of SWI/SNF and PcG complexes to proliferation-differentiation decisions, making use of the reproducible development of the nematode Caenorhabditis elegans. RNA interference, lineage-specific gene knockout, and targeted degradation of SWI/SNF BAF components induced either overproliferation or acute proliferation arrest of precursor cells, depending on residual protein levels. Our data show that a high SWI/SNF BAF dosage is needed to arrest cell division during differentiation and to oppose PcG-mediated repression. In contrast, a low SWI/SNF protein level is necessary to sustain cell proliferation and hyperplasia, even when PcG repression is blocked. These observations show that incomplete inactivation of SWI/SNF components can eliminate a tumor-suppressor activity while maintaining an essential transcription regulatory function.


Working at home stories: Presentation from Mike Boxem at the TAGC meeting

In the ”Mechanistic Intracellular Dynamics” session Mike Boxem presented the data of former PhD student Joao Ramalho and current PhD student Jorian Sepers. The presentation was entitled “ ERM-1 phosphorylation and NRFL-1 redundantly control lumen formation in the C. elegans intestine in concert with the Ste20-like kinase GCK-4”.

Mike

Working at home stories: Presentation at the TAGC meeting

Prof. Dr. Sander van den Heuvel was the first speaker of the “New Technology and Resources in Development (C.elegans)” session and gave a talk entitled : “Lineage-specific analysis of cell proliferation-differentiation control”. Due to the corona pandemic the conference was online and could be attended by everybody who registered beforehand. Because of that we all could (re)watch Sanders presentation online. During the opening talk they announced that 10000 people registered for the conference. This might be a new way of attending conferences, courses and summer schools in the (near) future.

Sander

Two positions available

The newly established research group of Dr Suzan Ruijtenberg is looking for a PhD candidate. The focus of the project is to visualize and understand when and where individual proteins are synthesized and how changes in translation efficiencies affect cell fate and organismal behavior.

More information about this position you find here and and about the research group here.

The Van den Heuvel lab is looking for a PhD or Postdoc candidate. The focus of the project will be to reveal the regulatory logic of cellular decision making in the context of animal development.

More information about this position you find here and and about the research group here.

Working at home stories: Journal club & friday afternoon borrel

From now on we close our working at home week with a journal club. We discuss shortly three papers. Afterwards we start the weekend with our virtual borrel.

Juliane

Working at home stories: Vincent Portegijs

I obviously can’t take care of the worms from the home office, so I go to the campus once or twice a week for the absolute essentials. It’s a luxury to be able to maintain animals and finish crosses that take weeks, so that the projects won’t be so delayed when we are able to work regular hours again. It also poses a challenge: how do we continue our lab projects when we can’t actively work on them? I’ve traded the lab bench for the dinner table. Rather than pipetting and worm picking I’m now focused on brainstorms on exciting genes, online meetings, thesis writing supervision and lots of planning ahead. For us lab tigers, it’s surprising how long the to-do list has become when being restricted to working from home. It poses an interesting new situation for the time being, but I’m already longing to go back to the daily bike ride, quick face to face discussions in the corridors, cappuccino trips with colleagues and even to wearing that labcoat on a warm summer day again.

Vincent

Publication in iScience

Juliane

Somitogenesis, the primary segmentation of the vertebrate embryo, is associated with oscillating genes that interact with a wave of cell differentiation. The necessity of cell-matrix adherence and embryonic tension, however, suggests that mechanical cues are also involved. To explicitly investigate this, Nelemans et al applied surplus axial strain to live chick embryos. Despite substantial deformations, the em-bryos developed normally and somite formation rate was unaffected. Surprisingly, however, we observed slow cellular reorganizations of the most elongated somites into two or more well-shaped daughter somites. In what appeared to be a regular process of boundary formation, somites divided and fibronectin was deposited in between. Cell counts and morphology indicated that cells from the somitocoel underwent mesenchymal-epithelial transition; this was supported by a Cellular Pottsmodel of somite division. Thus, although somitogenesis appeared to be extremely robust, we observed new boundary formation in existing somites and conclude that mechanical strain can bemorphologically instructive.


Working at home stories: Ben Nelemans

Nowadays, a large part of our work can be done behind every computer, and this time also challenges us to be creative in how we continue our work while working from home. As a teacher, I expand our existing materials on new platforms, for teaching digitally. This also involves innovating teaching material that was not digital before. At the moment, I am turning practicals into digital data sets and online instructions for my students. Many of the lectures will be done via video recordings. However, I miss the personal contact with colleagues and my students a lot! Video conferences also helps us in continuing meetings or social contacts, but it also shows me they do not give the same satisfaction as face to face meetings.

Ben

Publication in Plant Methods

Juliane

In collaboration with the Centre of Crop Systems analysis at Wageningen University and Research Centre, the Molecular Plant Physiology group at Utrecht University and our BioSorter facility we report on the development of a high throughput method for counting seeds and measuring individual seed sizes. Seed size and number are important plant traits from an ecological and horticultural/agronomic perspective. Until now research on seed size and number is limited by the absence of suitable high throughput phenotyping methods.The method uses a large-particle flow cytometer to count individual seeds and sort them according to size, allowing an average of 12,000 seeds/hour to be processed. Classification algorithms are used to refine the separation process in silico.


Working at home stories: Journal club

The upcoming weeks we will use this blog to show how working at home for us looks like. Instead of hours in the lab our time there is limited to finish experiments and to keep long term experiments running.

Last week we had our first virtual journal club. We got an update about the latest science news but also a little view on the current work place of our colleagues.

Juliane

Congratulations Sander van den Heuvel for receiving the NWO ENW GROOT grant

Prof. Dr. Sander van den Heuvel receives the NWO ENW GROOT grant to investigate Single Cell Analysis of Animal Development. NWO GROOT grant was initiated in 2017 and is intended for consortia in which research groups create added value through collaboration. Sander van den Heuvel is leading the consortium, where Kirsten ten Tusscher, Rik Korswagen and Alexander van Oudenaarden are part of.


Congratulations Dr. Joao Ramalho

Joao succesfully defended his thesis "Untangling the animal plumbing: Apical domain formation in C. elegans tubular epithelia".

Joao

Left: The cover of his PhD booklet. Middle: Joao just before defending his PhD thesis. Right: Joao with his paranimphs.


Goodbye Molly !!

We said goodbye and thank you to our PostDoc Molly with a lunch at the Basket. Molly worked for the past four years in the van den Heuvel group. Thank you Molly for all excellent work, good luck with your future plans and lets keep in touch.

Molly

Goodbye lunch for Molly at the Basket on the Utrecht Science Park.


Congratulations Dr. Ruben Schmidt

Ruben succesfully defended his thesis "Genetic and optogenetic analysis of cell cleavage plane positioning".

Ruben

Left: Ruben with his two paranymphs. Middle: Ruben got a 110 year old microscope from Zeiss as his graduation gift. Right: The cover of his PhD booklet.


Welcome Suzan!!

Suzan will start up her own research group that will focus on how translational regulation contributes to cellular behavior and developmental decisions, using a combination of genetic, biochemical and single molecule imaging approaches.

Suzan

Suzan did a very succesful PhD in the van den Heuvel group, followed by a PostDoc at the Tannenbaum groep at the Hubrecht Insitute. Her postdoc was financial supported with a Veni grant she recieved in 2016.


Review in Current Opinion of Cell Biology

Janine_Sander

Tissue polarity in C. elegans is organized by Wnt-signaling with some resemblance to the Wnt/planar cell polarity (PCP) pathway in other organisms. Even though they lack core PCP protein functions, these conserved PCP are able to regulate directed cell migratory events in C. elegans. Janine and Sander discuss the latest insights and use of C. elegans as a PCP model.


Publication in Development

Suzanne

The mechanism that determines whether cells undergo symmetric or asymmetric cell division is poorly understood. Van der Horst et al studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. These seam cells go through a reproducible pattern of asymmetric divisions and symmetric divisions that increase the seam cell number. The authors show using time-lapse fluorescence microscopy that the conserved Runx/CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression.


Congratulations Dr. Vincent Portegijs

Vincent succesfully defended his thesis "Developmental control of the C. elegans cell cycle".

Vincent

Left: Vincent with his promoter Prof. Dr. Sander van den Heuvel and Right: The cover of his PhD booklet.


Goodbye Helena !!

We said goodbye and thank you to our PostDoc Helena with a lunch joined by plenty of laughs and fun talks. Helena worked for the past five years in the Boxem group. With Helena around, the lab was always filled with laughs and support. Thank you Helena for all your good work, good luck with your future plans and lets keep in touch.

helena

Goodbye lunch at the pancake restaurant in Bunnik.

Review in Current Opinion of Cell Biology

Amalia_Victoria

Polarization of epithelial cells is orchestrated by a network of conserved polarity regulators that establish opposing cortical domains through mutually antagonistic interactions and positive feedback loops. The authors highlight recent findings on the mechanisms that control the activity and localization of apical–basal polarity regulators, including oligomerization and higher order complex formation, auto-inhibitory interactions, and electrostatic interactions with the plasma membrane.


Congratulations Dr. Suzanne van der Horst

Suzanne succesfully defended her thesis "In vivo" studies of stem cell-like divisions of C.elegans.


Dispatch in Current Biology

mike_sander

Polarity establishment is a key developmental process, but what determines its timing is poorly understood. Boxem and Heuvel discuss new research in Caenorhabditis elegans demonstrates that the PAR polarity system extensively reconfigures before becoming competent to polarize. By inhibiting membrane localization of anterior PAR proteins, AIR-1 (aurora A) and PLK-1 (polo kinase) prevent premature polarization.


Welcome Tessa !!

Tessa joined the van den Heuvel group as a PostDoc. She did her PhD in the Lab of Caroline Hill at the Francis Crick Institute studying the mechanism of SMAD-mediated transcription on chromatin response to Activin/Nodal signalling.

Tessa

Afterwards she continued as a PostDoc in the Julie Ahringer Lab in Cambridge to investigate heterochromatin during C.elegans development and aging.


Review in Genetics

sander_review

In this review they focus on the regulation of the cell cycle in the context of C. elegans development, with reference to other systems, with the goal of better understanding how cell cycle regulation is linked to animal development in general.


Review in Current Opinion in System Biology

mike_review

Sanne and Mike review the state of interactome mapping in C. elegans,and discuss recent developments that arelikely to improve protein interaction mapping efforts inthis organism in the coming years


Happy Holidays

Our yearly Christmas dinner took as usual place at Sander and Inge’s place in Bilthoven. The traditional potpourrie dinner including a huge turkey made by Sander was a big succes. This year we also started a new tradition…the ugly Christmas sweater tradition.

Jorian

Goodbye Jana !!

We said goodbye and thank you to Jana with a lovely borrel. Jana worked in our lab for several years in the boxem group. She saw plenty of students, PhDs and Postdocs joining and leaving the lab. Now it was her time as she decided to retire and enjoy her passion for traveling and visiting her family living abroad. Thank you Jana for all your good work and lets keep in touch.

Jorian

Amalia and Victoria visit New York University in Abu Dhabi

Amalia and Victoria visited New York University in Abu Dhabi (NYUAD) where they carried out their secondments in the lab of Dr. Kris Gunsalus. There, they took advantage of using a robotic platform to perform two whole-genome RNAi screens in C. elegans. The goal of the screens was to identify proteins that act redundantly with two major polarity regulators, the proteins lgl-1 and Crbs. “It was a great experience. In Abu Dhabi we had the opportunity to learn more about the Arabic culture and at the same time to explore unforeseen technological tools that really work on the favor of scientific progress” Amalia says. Victoria: “For this great experience, it’s important to thank Hala Fahs, Fathima Mohammed Refai and Suma Gopinadha that welcomed and helped us during the whole procedure. In Abu Dhabi, we managed to complete 2 screens in only one month, an experiment that would have taken more than four months without the robot.”

amalia_vic

On the left panel, Victoria is loading the 96well plates on the robot; center panel depicts the robot; on the right panel Amalia is watching operation of the robot from the computer screens.

Welcome Jorian !!

Jorian Sepers joined the Boxem group as a PhD student. Jorian did his B.Sc in Biology and his M.Sc in Molecular and Cellular Life Sciences at the Utrecht University. He has previous been a student in the Boxem group doing research on the isoforms of PAR-3 and PAR-6 in C. elegans epithelia. For a second intershipt he went to the Lab of David Bilder at University of California Berkeley and investigated polarity deficient ovarian tumors in Drosophila melanogaster flies.

Jorian

Congratulations Dr. Ben Nelemans

Ben succesfully defended his thesis "Exploring mechanobiology of somie formation in the chicken embryo".

Ben

Left: Ben just before he gets his degree and Right: The cover of his PhD booklet.

Congratulations Dr. Lars Fielmich

Lars succesfully defended his thesis "Pullin apart mitotic spindel positioning in C. elegans early embryo".

Lars

Left: Lars gave a presentation about his PhD work to colleagues,friends and family. Right: Cover of his PhD booklet.


Welcome Jason!!

Jason Kroll joined the Boxem group as a Posdoctoral fellow. Jason did his PhD at the Universiy of California in the Department of Moelcular and Cell Biology working on genetic suppression of epilepsy and seizures in Drosophila. Afterword he did a Post Doc on cell fate decisions in C. elegans in the group of Jeroen van Zon at AMOLF.

Jason

Publication in Elife

Lars_Ruben

Spindle positioning is driven by dynein-mediated pulling forces exerted on astral microtubules, which requires an evolutionarily conserved complex .To examine individual functions of the complex components, we developed a genetic strategy for light-controlled localization of endogenous proteins in C. elegans embryos. Fielmich and Schmidt were able to define one part of the complex as a regulatable membrane anchor, and a second part as a potent activator of dynein-dependent spindle-positioning forces.


EMBO workshop C. elegans Developmental, Cell Biology and Gene expression & European C.elegans meeting 2018

NWO

A large part of our group joined the bi-annual meetings in Barcelona. During the 5-day meeting we could share our research projects and results in presentation and poster sessions. All participants were impressed and came back with plenty of input and new ideas.

CSND (Cancel and Stem Cells developmental Biology) PhD retreat 2018

NWO

The yearly 3-day meeting is organized from for PhD students. This year Amalia was in the organizing committee and set up a schedule full of (poster, laptop) presentation combined with fun activities like an obstacle bouncing castle.


Welcome Ben!!

Ben Nelemans joined the Developmental Biology department to support the teaching crew.

Ben

Publication in PNAS

Lars _japan

Mutations in the adenomatous polyposis coli (APC) are frequently associated with colorectal cancers in humans. As its role in stabilizing microtubules during cell division is largely unknown, live imaging, laser microsurgery, and numerical simulation were performed. Together with the group of Hitoshi Sawa Fielmich document a mechanical role for the APC protein and provides a physical basis for spindle-pulling force attenuation.


Review in Journal of Molecular Biology

Review Helena

Protein interactions are central to the control of cell polarity. Several interactions have been identiefied, however the underlaying dynamics and molecular mechanismto control these interaction are not well understood. Particular helpful are systemactic large-scale protein-protein interaction mapping approaches. Pires and Boxem discuss commonly used methods used to generate proteome-wide interactome maps.


Welcome Sanne!!

Sanne Remmelzwaal joined the Boxem group as a PhD student. We wish you a good start and a succesful time.

Sanne

Welcome Amir!!

Amir Homavar joined the van den Heuvel group as a PhD student. We wish you a good start and a succesful time.

Amir

Publication in JCB- The Journal of Cell Biology

Ruben Publication

In animal cells the position of the mitotic spindle is tightly regulated as it determines the plane and orientation of cell devision. Using fluorescently labelled endogenous proteins Schmidt and Co-worker show that dynein exists in two distinct cortical populations indicating the excisting of two mechanism that together create a highly robust force-genertating system.


21st International C.elegans Conference 2017

la

Joao , Molly , Suzanne , Lars ,and Mike attented the bi-annual genetics meeting of C.elegans. Suzanne and Lars were chosen to present their data in form of a presentation (picture bottom row). Joao and Molly presented their data during the Poster session. Guided were the busy and long days by a conference dinnner/party and a baseball game


Dinner with Geraldine Seydoux

Geraldine Seydoux

Geraldine Seydoux was invited to give a Seminar at the Cancer, Stem Cell and Developmental Biology PhD and Master programme . Her lab wants to understand how single cell eggs develop into complex multicellular embryo. In the evening she joined our group for dinner at the yearly POP-up restaurant de Maaltuin at the botanical garden.


EMBO Meeting 2017 Cell Polarity and membrane dynamics 2017

NWO

07-4-2017:

Amalia , Victoria , Helena and Mike joined the EMBO meeting. While the Helena, Victoria and Amalia presented their data during the Poster session, Mike gave an presentation about Regulation of ERM proteins


Positions available

PhD and PostDoc positions have become available in the group of Mike Boxem. Click here for details.


Award for Suzanne van der Horst at the meeting of the Dutch Society for Stem Cell Research 2017

NWO

04-11-2017: Suzanne won the 2nd price with her presentation "Understanding a stem cell divison pattern in C. elegans". She was rewarded with a 500€ travel grant. Congratulations!


Vici Grant for Mike Boxem

NWO

02-17-2017: Mike Boxem was awarded an NWO Vici Grant for his proposal "Deciphering the systems that control epithelial cell polarity". Congratulations!


ZonMW Top Grant for Sander van den Heuvel

ZonMW

02-03-2017: Sander van den Heuvel (UU Developmental Biology), Casper Hoogenraad (UU Cell Biology), and Eva van Rooij (Hubrecht Institute) were awarded a ZonMW TOP Grant for their proposal "Cell division arrest and self-renewal potential of differentiated neurons and heart muscle cells". Congratulations!


Molly wins EMBO Long-Term Fellowship Award

Molly Godfrey, who joined our group this year as a Postdoc succesfully applied for the EMBO Long-Term fellowship. Congratulation Molly, we are very proud of you.

Molly's project will deepen our knowledge of the regulation of cell cycle exit during differentiation. The interplay between cell cycle regulators and chromatin factors during cell cycle exit will be investigated, examining how chromatin factors control cell cycle gene expression, and whether cell cycle regulators reciprocally regulate chromatin factors. This research will have important implications in the contexts of developmental biology, regeneration studies, and cancer research.


PolarNet Kickoff meeting in November

PolarNet Kickoff picture

Amalia , Victoria and Janine are part of the PolarNet ITN. PIs and all PhD studenst presented their research plans and first results at the international meeting in Utrecht.


Lunch with Nobel Prize winner Martin Chalfie

Martin Chalfie

Martin Chalfie was the Keynote Speaker at the Science for Life conference and impressed everybody with an inspiring talk not just about GFP. The next day we had the honour to talk to him during an informal lunch. Thanks again. We really appreciate that you took the time answering all our questions.


Lars Fielmich won award for best presentation at the Science for Life

Lars presentation

Lars presented part of his Phd work at the conference. Among all presenters he was awarded with a price for the best given presentation in his session. Congratulations !!


Tijs Koorman wins best PhD publication of the academic year 2015/2016

Tijs Publication

Former PhD student of Mike Boxem Tijs Koorman was awarded with the price for the best PhD publication of the academic year 2015/2016. Koorman and Co-worker published in Nature Cell Biology. They used a large-scale protein interacting mapping combined with systematic phenotypic profiling to study the netwerk of physical interactions that underlies polarity establishment and maintenance in C. elegans. Congratulation Tijs


Publication in Plos Genetics

Vincent Publication

Portegijs and Co-worker data show that phosphorylation of multiple LIN-5 domains by different kinases contributes to a mechanism for spatiotemporal control of spindle positioning and chromosome segregation.


Dutch BioPhysics meeting 2016

Members of the Boxem and van den Heuvel Lab presented their data at the yearly Dutch Biophysics 2016 meeting in Veldhoven.

Lars Veldhoven

Lars at the end of his presentation Shedding light on mitotic spindle positioning in asymmetric cell division


Commentary

Aniek Publication

Aniek van der Vaart and Sander van den Heuvel were asked to comment on the recent publication of Sun et al (Cell Stem Cell, 2016). Sun and co-workers findings provide new insight in the control of terminal differentiation and suggest strategies to promote tissue repair.


Publication in BMC Biology

Waijers Publication

Waaijers, former PhD student of Mike Boxem, and Co-workers present in the paper an in vivo biotinylation-based approach for the tissue-specific purification of protein complexes from Caenorhabditis elegans.


Welcome Amalia and Victoria !!

Amalia Riga and Victoria Garcia Castiglioni joined the Boxem group as PhD students. Amalia and Victoria are part of the PolarNet a European research and training consortium. We wish both a good start and a succesful time.

Left: Amalia did her Master of Science at the University of Crete. Right: Victoria did her Master of Science at the Universistat Autonoma de Barcelona


Developmental Biology

The research of the Developmental Biology division focuses on studying biological principles in the context of living, developing multicellular organisms. The division is led by Prof. Dr. Sander van den Heuvel, and is home to several research groups, each with their own research focus.

Sander van den Heuvel studies the regulation of cell division in the context of animal development. Research topics in the group include asymmetric cell division, the control of cell-cycle entry, and the regulation of differentiation vs. proliferation. C. elegans is the main model system used for these studies, with less frequent use of mammalian tissue culture systems.

Mike Boxem uses a combination of systems biology approaches, systematic experimental manipulation, and live-cell imaging to study the process of cell polarization.

Rüdiger Schulz studies basic questions regarding the control of spermatogonial stem cell divisions in Zebrafish, as well as applied questions on the reproduction of commercial fish including Salmon and Cod.

Inge The studies the regulation of cell proliferation vs. differentiation in collaboration with the group of Sander van den Heuvel.

Suzan Ruijtenberg studies how translational regulation contributes to cellular behavior and developmental decisions, using a combination of genetic, biochemical and single molecule imaging approaches.

To read more about the different research projects, please visit the research group sites through the menu on the right.