Close

An early cell shape transition drives evolutionary expansion of the human forebrain

Silvia Benito-Kwiecinski, Stefano L. Giandomenico, Magdalena Sutcliffe, Erlend S. Riis, Paula Freire-Pritchett, Iva Kelava, Stephanie Wunderlich, Ulrich Martin, Greg Wray, Madeline A. Lancaster

Posted on: 31 July 2020

Preprint posted on 4 July 2020

Article now published in Cell at http://dx.doi.org/10.1016/j.cell.2021.02.050

How Humans Got Big Brains: A delayed cell-state transition in neurogenesis leads to a larger human brain

Selected by Monica Tambalo, Teresa Rayon, Maiko Kitaoka

Background

How has the human brain evolved its unique features? Such a fascinating question remains yet widely unexplored. Among the human brain’s remarkable features, its size is perhaps one of the most evident, with roughly a 3-fold increase in human brain size compared to chimpanzee and gorilla. A conspicuous amount of studies, mainly using rodent model systems, have contributed to our current understanding of brain embryonic development. Such approaches are excellent to teach us about conserved mechanisms but are not suitable for informing on human specific brain features and primate evolution.

A revolutionary approach to study human brain development and its evolution has been the advent of human brain organoids derived from human pluripotent stem cells [1],[2], and the invaluable possibility of extending this approach to virtually any species.

A fundamental process in brain development is neurogenesis. Within the cerebral cortex a neurogenic precursor, also known as neuroepithelial (NE) cell, is characterized by a columnar morphology and divides symmetrically during its proliferative phase. This proliferation is essential for the enlargement of the neocortex in primates. NE cells are highly epithelial, with tight and adherens junctions at their apical surface. NE progenitors will then transition into neurogenic radial glia (RG) by losing epithelial features, thinning and elongating the bipolar processes, and switching to asymmetric cell divisions, where one daughter cell self-maintains itself as RG and the other starts the neurogenic differentiation. This mechanism has been mainly studied using murine models while little is known about how it works in apes. Correlative evidence points to early changes in NE behaviour as a key mechanism for human cortical expansion, however direct evidence is poor.

To address directly this issue, Benito-Kwiecinski, Giandomenico, and colleagues [3] derived brain organoids from human, gorilla and chimpanzee and directly compared their neurogenetic properties, prior to neuron formation. This approach has given the authors the advantage of manipulating candidate genes and the ability to address their involvement in human and ape brain evolution.

(Top panels) 5-week organoids stained for neural progenitor marker SOX2 (red), dorsal telencephalic/intermediate progenitor marker TBR2 (grey), neuronal markers TUJ1 (human) and HuCD (gorilla) in yellow, and DAPI (blue) showing human derived organoids become larger in overall size than gorilla and chimpanzee organoids. Scale bar: 1 mm. From Figure 1A.

(Lower panels) Schematic summarizing the morphological changes in neural progenitor cells observed in human and gorilla organoids. Progenitor cells of both species undergo a gradual transition from NE to tNE to RG-like shapes. Human cells maintain columnar NE-characteristics for a longer period while gorilla cells show tNE morphologies (blue background) earlier than human. From Figure 2H.

Key points

  • The authors developed comparable human, gorilla and chimpanzee brain organoids to study NE development prior to the onset of neurogenesis. Perhaps as expected, human brain organoids were consistently larger than the gorilla or chimp organoids.
  • Human organoids show an enlarged ventricular apical surface at early stages of NE expansion, before the onset of neurogenesis.
  • The transition from NE (non neurogenic) to RG (neurogenic) in human and ape occurs during several days, and ape NE cells make this transition more rapidly than human.
  • Cell shape changes occur before the change in cell identity and before the onset of neurogenesis.
  • Identification of a new intermediate cell morphology state, the tNE.
  • By comparing RNA-seq data from each species, they focused on the differential expression of the ZEB2 gene, particularly due to its well-known role as a key mediator of the EMT transition and found that the ZEB2 gene drives the NE to RG transition.
  • Delayed onset of ZEB2 expression extends the NE stage, compared to ape, and may be a major contributor to neocortical expansion in humans
  • They generated an inducible-ZEB2 human brain organoid, demonstrating the powerful advantages of organoids to allow unprecedented control to manipulate genes involved in neurogenesis. By overexpressing human ZEB2 prematurely to match the expression levels and timing of gorilla organoids, the authors could trigger an earlier NE transition that led to a nonhuman, ape-like organoid morphology! This suggests that ZEB2 is a key regulator of species-specific brain development.

Things we like

This work elegantly demonstrates how the evolution of the neocortex can be studied systematically and quantitatively comparing stem cell models/organoids across species, providing perturbations that wouldn’t be feasible in human embryos. Previous 2D and 3D comparisons using stem cell models of primate cortical development had primarily focused on the differences in composition and proliferation rates of radial glial cells (RG) of macaque, human and chimpanzees [4]–[7]. Instead, this work centres its attention on the role of NE cells in cortical expansion for the first time and adds gorilla stem cells to the primate cerebral organoid zoo. Finally, we really appreciate that this work applies a classical embryology approach to organoids, where the authors start from a morphological observation and have begun to pin down the molecular mechanism.

Questions for the authors 

Q1. How complex was it to establish reliable differentiation protocols for human, gorilla and chimpanzee brain organoids? And how consistent were the phenotypes observed across cell lines?

Q2. Is ZEB2 regulated differently in gorilla vs human vs chimp? How so? Ie, what triggers its expression, and how might this be regulated in a species-specific way?

Q3. Mutations in the ZEB2 gene cause Mowat-Wilson syndrome. Do the authors think that the early role that they uncovered for ZEB2 is related to the microcephaly and intellectual disability of the patients?

Q4. Mutations in the ZEB2 gene cause Mowat-Wilson syndrome. Do the authors think that the early role that they uncovered for ZEB2 is related to the microcephaly and intellectual disability of the patients?

Q5. Considering the exceptional current times, it has been challenging for everyone to work from home at a usual pace. How was the process of writing this preprint during lockdown?

References

  1. Lancaster, M. A.; Knoblich, J. A. Generation of Cerebral Organoids from Human Pluripotent Stem Cells. Nat. Protoc. 2014, 9 (10), 2329–2340. https://doi.org/10.1038/nprot.2014.158.
  2. Lancaster, M. A.; Renner, M.; Martin, C. A.; Wenzel, D.; Bicknell, L. S.; Hurles, M. E.; Homfray, T.; Penninger, J. M.; Jackson, A. P.; Knoblich, J. A. Cerebral Organoids Model Human Brain Development and Microcephaly. Nature 2013, 501 (7467), 373–379. https://doi.org/10.1038/nature12517.
  3. Benito-Kwiecinski, S.; Giandomenico, S. L.; Sutcliffe, M.; Riis, E. S.; Freire-Pritchett, P.; Kelava, I.; Wunderlich, S.; Martin, U.; Wray, G. A.; Lancaster, M. A. An Early Cell Shape Transition Drives Evolutionary Expansion of the Human Forebrain. bioRxiv 2020, 2020.07.04.188078. https://doi.org/10.1101/2020.07.04.188078.
  4. Neurogenesis, C.; Fiddes, I. T.; Lodewijk, G. A.; Mooring, M.; Salama, S. R.; Jacobs, F. M. J.; Haussler, D.; Fiddes, I. T.; Lodewijk, G. A.; Mooring, M.; Bosworth, C. M.; Ewing, A. D. Human-Specific NOTCH2NL Genes Affect Notch Article Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis. Cell 2018, 173 (6), 1356-1369.e22. https://doi.org/10.1016/j.cell.2018.03.051.
  5. Otani, T.; Marchetto, M. C.; Gage, F. H.; Simons, B. D.; Livesey, F. J.; Otani, T.; Marchetto, M. C.; Gage, F. H.; Simons, B. D.; Livesey, F. J. 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size Article 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size. Stem Cell 2016, 18 (4), 467–480. https://doi.org/10.1016/j.stem.2016.03.003.
  6. Suzuki, I. K.; Gacquer, D.; Heurck, R. Van; Polleux, F.; Detours, V.; Vanderhaeghen, P. Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta / Notch Regulation Article Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta / Notch Regulation. 2018, 1370–1384. https://doi.org/10.1016/j.cell.2018.03.067.
  7. Pollen, A. A.; Bhaduri, A.; Andrews, M. G.; Nowakowski, T. J.; Meyerson, O. S.; Mostajo-Radji, M. A.; Di Lullo, E.; Alvarado, B.; Bedolli, M.; Dougherty, M. L.; Fiddes, I. T.; Kronenberg, Z. N.; Shuga, J.; Leyrat, A. A.; West, J. A.; Bershteyn, M.; Lowe, C. B.; Pavlovic, B. J.; Salama, S. R.; Haussler, D.; Eichler, E. E.; Kriegstein, A. R. Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution. Cell 2019, 176 (4), 743-756.e17. https://doi.org/10.1016/j.cell.2019.01.017.

 

Tags: brain organoids, evodevo, neurodevelopment

doi: https://doi.org/10.1242/prelights.23633

Read preprint (No Ratings Yet)

shared

Q1. How complex was it to establish reliable differentiation protocols for human, gorilla and chimpanzee brain organoids? And how consistent were the phenotypes observed across cell lines?

The author team

We have found that regardless of species, any given pluripotent stem cell (PSC) line can produce brain organoids, as long as it successfully undergoes neural differentiation. However, like many others in the field, we have observed that some PSC lines simply do not reliably generate neural identity, and are therefore not adequate for brain organoid differentiation. Indeed, several reports have indicated epigenetic and transcriptional signatures (Kim et al., 2011) and developmental biases (Strano et al., 2020) that cause some PSC lines to be restricted in their differentiation ability. Thus, we screened several cell lines from both human and non-human apes, and ultimately only used those that reliably formed neural tissues, while also paying attention to the sex of the cell lines (all lines used in our study were female) so as not to introduce confounding variables.

With the different species PSC lines, we sought to use identical protocols, both in terms of culture conditions (media formulation, number of cells seeded, etc.) and timing. However, while culture conditions did not have to be adjusted uniquely for the different species, we found that the earliest stage of organoid differentiation, namely the embryoid body (EB) stage, had to be slightly sped up for chimpanzee PSCs.  This was evident in the morphology, and quantity of non-neural tissue produced. We found that if we followed the human timing with chimpanzee PSCs, non-ectodermal lineages developed during the EB stage into more differentiated cell fates prior to neural induction. To correct this, we simply moved chimpanzee EBs to neural induction two days earlier than the other apes. This is very interesting given the more rapid gestation of chimpanzees (34 weeks).

Kim, K., Zhao, R., Doi, A., Ng, K., Unternaehrer, J., Cahan, P., Hongguang, H., Loh, Y.H., Aryee, M.J., Lensch, M.W., et al. (2011). Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells. Nat. Biotechnol. 29, 1117–1119.

Strano, A., Tuck, E., Stubbs, V.E., Livesey, F.J. (2020). Variable Outcomes in Neural Differentiation of Human PSCs Arise from Intrinsic Differences in Developmental Signaling Pathways. Cell Rep. 31, 107732.

Q2. Is ZEB2 regulated differently in gorilla vs human vs chimp? How so? Ie, what triggers its expression, and how might this be regulated in a species-specific way?

The author team

At present we don’t know what signalling pathway is upstream of ZEB2 but appealing candidates would be FGF family members, as they play key roles early in neurodevelopment and have the potential to induce ZEB2 expression (JeongGoo, L. et al, 2018). ZEB2 is a very interesting gene in the context of neurodevelopment as it has been shown to be involved in a number of processes ranging from pluripotency exit to axon pathfinding and myelination. The ZEB2 locus contains and is surrounded by a number of human accelerated regions, sequences of the genome that show extremely high conservation across vertebrates but are strikingly different in humans. In addition, recent single-cell ATAC-seq experiments (Kanton, S. et al, 2019) have revealed a number of differentially accessible genomic regions between human and chimp organoids, suggesting that the gene is differentially regulated in these two species. Thus, changes in the enhancer and silencer regions associated with ZEB2 might orchestrate the different expression dynamics we observed in human and gorilla brain organoids. While genomic-level differences are the obvious suspect, it should not be ruled out that differences in ZEB2 expression could potentially also come down to changes in post-transcriptional regulation. For example, the 3’ UTR of ZEB2 is recognised by miRNAs of the miR-200 family both in the context of metastasis and neurogenesis (Hill, L. et al., 2013, Yang, S. et al., 2018).

Yang, S., Toledo, E.M., Rosmaninho, P. et al. A Zeb2-miR-200c loop controls midbrain dopaminergic neuron neurogenesis and migration. Commun Biol 1, 75 (2018). https://doi.org/10.1038/s42003-018-0080-0

Louise Hill , Gareth Browne, Eugene Tulchinsky. ZEB/miR-200 feedback loop: at the crossroads of signal transduction in cancer. Int J Cancer 132(4):745-54 (2013).

JeongGoo Lee, Eric Jung and Martin Heur. Fibroblast growth factor 2 induces proliferation and fibrosis via SNAI1-mediated activation of CDK2 and ZEB1 in corneal endothelium. Journal of Biological Chemistry 293(10): 3758–3769 (2018).

Kanton, S., Boyle, M.J., He, Z. et al. Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature 574, 418–422 (2019). https://doi.org/10.1038/s41586-019-1654-9

Q3. Mutations in the ZEB2 gene cause Mowat-Wilson syndrome. Do the authors think that the early role that they uncovered for ZEB2 is related to the microcephaly and intellectual disability of the patients?

The author team

In our study we tested the effect of ZEB2 heterozygous loss-of function on brain organoid development. In this background early in brain organoid development we observed an upregulation in epithelial cell-cell junction markers including E-cadherin and Occludin. Concomitantly, we saw a decrease in the number of TBR2+ intermediate progenitor cells produced. We did not explore the long-term effect of these changes but they are likely to have an impact on the overall organoid neuronal output.

Mowat-Wilson syndrome (MWS) is a complex disorder that manifests itself as an array of brain developmental defects with variable penetrance. This complex pathology is caused by de novo heterozygous loss-of-function mutations including nonsense mutations, frameshift mutations, and deletions in ZEB2. Although we were primarily interested in the evolutionary role of ZEB2, the mutation we introduced to test for a role in early neuroepithelial differentiation mimicked that seen in patients with MWS. Thus, it may well be that our model captures certain aspects of the pathology, but more work would be needed to conclusively say. Having said this, the early role that we uncovered for ZEB2 is likely to have important implications for brain size determination and neuronal output. Therefore, it is not unreasonable to speculate that ZEB2 mutations that lead to impairment of this neurodevelopmental process in humans could contribute to MWS pathogenesis.

Q4. Mutations in the ZEB2 gene cause Mowat-Wilson syndrome. Do the authors think that the early role that they uncovered for ZEB2 is related to the microcephaly and intellectual disability of the patients?

The author team

It would be difficult both technically and ethically to study this process in vivo in human or ape embryos. First, the behaviour of neural progenitor cells we have characterized occurs at early pre-neurogenic stages in fetal development, corresponding to less than a month post-conception – a stage where many mothers are not even aware of their pregnancy. Although it is possible to culture primary brain tissue as an organotypic slice culture (Subramanian et al., 2017), samples have not been collected early enough to observe pre-neurogenesis stages where neural progenitor cells would still be purely expanding in behaviour and neuroepithelial in morphology. Second, it is unethical to experiment on apes, given their protected status, so a study of ape embryos would be impossible at any stage, unless through a spontaneous abortion, which is rare and difficult to acquire intact. Thus, although it would be highly beneficial to confirm our findings with primary specimens, evidence from later stage organoids suggests a high degree of overlap with in vivo development (Camp et al., 2015; Luo et al., 2016) suggesting that it is a safe assumption that the rest of the self-organization process of brain organoid formation follows human brain development with a high fidelity. Therefore, brain organoids offer a window into an otherwise black box in human and ape brain development.

Camp, J.G., Badsha, F., Florio, M., Kanton, S., Gerber, T., Wilsch-Bräuninger, M., Lewitus, E., Sykes, A., Hevers, W., Lancaster, M., et al. (2015). Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc. Natl. Acad. Sci. U. S. A. 112, 15672–15677.

Luo, C., Lancaster, M.A., Castanon, R., Nery, J.R., Knoblich, J.A., Ecker, J.R. (2016). Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain. Cell Rep. 17, 3369-3384.

Subramanian, L., Bershteyn, M., Paredes, M.F., and Kriegstein, A.R. (2017). Dynamic behaviour of human neuroepithelial cells in the developing forebrain. Nat. Commun. 8.

Q5. Considering the exceptional current times, it has been challenging for everyone to work from home at a usual pace. How was the process of writing this preprint during lockdown?

S.B-K.: It was a little challenging to convert the home into a workplace and get used to writing from a kitchen chair versus a comfortable library seat. But the writing-up process fortunately did not require physical access to the lab and we had great communication throughout via regular Zoom meetings and e-mail correspondence.

S.L.G.: They were certainly trying times but I feel that having the manuscript to focus on was an extremely fortunate coincidence. Working in a team with Madeline and Silvia and the other authors, having regular meetings and deadlines, really helped me to deal with the daily struggles and keep spirits high.

M.A.L.: Like many with small children, I found it quite challenging to juggle childcare and work. And finding a solid chunk of time for writing was often very difficult. But thankfully, I have an amazing team, and Silvia and Stefano (the co-first authors) worked together beautifully, making the writing process for this manuscript seamless.

1 comment

3 years

Sheila Garcia-Rosa

How long it took to develop this work, from the experimental design to the final experiment?

Have your say

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

Also in the developmental biology category:

Specialized signaling centers direct cell fate and spatial organization in a limb organoid model

Evangelia Skoufa, Jixing Zhong, Oliver Kahre, et al.

Selected by 05 September 2024

Ryan Harrison

Developmental Biology

Adult caudal fin shape is imprinted in the embryonic fin fold

Eric Surette, Joan Donahue, Stephanie Robinson, et al.

Selected by 28 August 2024

Isabella Cisneros

Developmental Biology

TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development

Canan Doganli, Daniel A. Baird, Yeasmeen Ali, et al.

Selected by 16 August 2024

Reinier Prosee

Developmental Biology

Also in the evolutionary biology category:

Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium

Nikolai Hecker , Niklas Kempynck , David Mauduit, et al.

Selected by 02 July 2024

Rodrigo Senovilla-Ganzo

Bioinformatics

Modular control of time and space during vertebrate axis segmentation

Ali Seleit, Ian Brettell, Tomas Fitzgerald, et al.

AND

Natural genetic variation quantitatively regulates heart rate and dimension

Jakob Gierten, Bettina Welz, Tomas Fitzgerald, et al.

Selected by 24 June 2024

Girish Kale, Jennifer Ann Black

Developmental Biology

Fetal brain response to maternal inflammation requires microglia

Bridget Elaine LaMonica Ostrem, Nuria Dominguez Iturza, Jeffrey Stogsdill, et al.

Selected by 24 April 2024

Manuel Lessi

Neuroscience

Also in the neuroscience category:

The RNA binding protein HNRNPA2B1 regulates RNA abundance and motor protein activity in neurites

Joelle Lo, Katherine F. Vaeth, Gurprit Bhardwaj, et al.

Selected by 24 September 2024

Felipe Del Valle Batalla

Neuroscience

Pharyngeal neuronal mechanisms governing sour taste perception in Drosophila melanogaster

Bhanu Shrestha, Jiun Sang, Suman Rimal, et al.

Selected by 23 September 2024

Matthew Davies

Cell Biology

Triglyceride metabolism controls inflammation and APOE4-associated disease states in microglia

Roxan A. Stephenson, Kory R. Johnson, Linling Cheng, et al.

Selected by 22 August 2024

Gustavo Stelzer, Marcus Oliveira

Biochemistry

preLists in the developmental biology category:

BSDB/GenSoc Spring Meeting 2024

A list of preprints highlighted at the British Society for Developmental Biology and Genetics Society joint Spring meeting 2024 at Warwick, UK.

 



List by Joyce Yu, Katherine Brown

GfE/ DSDB meeting 2024

This preList highlights the preprints discussed at the 2024 joint German and Dutch developmental biology societies meeting that took place in March 2024 in Osnabrück, Germany.

 



List by Joyce Yu

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)

 



List by Nándor Lipták

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020

 



List by Jesus Victorino

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.

 



List by Alex Eve

Society for Developmental Biology 79th Annual Meeting

Preprints at SDB 2020

 



List by Irepan Salvador-Martinez, Martin Estermann

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EDBC Alicante 2019

Preprints presented at the European Developmental Biology Congress (EDBC) in Alicante, October 23-26 2019.

 



List by Sergio Menchero et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.

 



List by Alex Eve

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London

 



List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.

 



List by Alexa Sadier

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.

 



List by Shikha Nayar

Also in the evolutionary biology category:

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

EMBO | EMBL Symposium: The organism and its environment

This preList contains preprints discussed during the 'EMBO | EMBL Symposium: The organism and its environment', organised at EMBL Heidelberg, Germany (May 2023).

 



List by Girish Kale

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

COVID-19 / SARS-CoV-2 preprints

List of important preprints dealing with the ongoing coronavirus outbreak. See http://covidpreprints.com for additional resources and timeline, and https://connect.biorxiv.org/relate/content/181 for full list of bioRxiv and medRxiv preprints on this topic

 



List by Dey Lab, Zhang-He Goh

1

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.

 



List by Alex Eve

Pattern formation during development

The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.

 



List by Alexa Sadier

Also in the neuroscience category:

2024 Hypothalamus GRC

This 2024 Hypothalamus GRC (Gordon Research Conference) preList offers an overview of cutting-edge research focused on the hypothalamus, a critical brain region involved in regulating homeostasis, behavior, and neuroendocrine functions. The studies included cover a range of topics, including neural circuits, molecular mechanisms, and the role of the hypothalamus in health and disease. This collection highlights some of the latest advances in understanding hypothalamic function, with potential implications for treating disorders such as obesity, stress, and metabolic diseases.

 



List by Nathalie Krauth

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

SDB 78th Annual Meeting 2019

A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.

 



List by Alex Eve

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Young Embryologist Network Conference 2019

Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London

 



List by Alex Eve
Close