Mastodawn

Development Jun 20, 2023

Oncogene overexpression accelerates heart regeneration

Read this Research Highlight showcasing work from Catherine Pfefferli, Anna Jaźwińska and colleagues from University of Fribourg:

https://journals.biologists.com/dev/article/150/12/e150_e1201/316741/Oncogene-overexpression-accelerates-heart

Read the Stem Cells and Regeneration Article 'Parallels between oncogene-driven cardiac hyperplasia and heart regeneration in zebrafish' here:

https://journals.biologists.com/dev/article/150/12/dev201412/316736/Parallels-between-oncogene-driven-cardiac

Oncogene overexpression accelerates heart regeneration

The post-mitotic nature of adult human cardiomyocytes means that our risk of heart tumours is low. By contrast, adult zebrafish hearts can undergo cardiomyocyte proliferation to regenerate damaged tissue, but it is unknown if they respond to oncogene expression. Here, Anna Jaźwińska and colleagues generate a zebrafish model for reversibly inducing expression of the HRASG12V oncogene in zebrafish cardiomyocytes. They find that HRASG12V overexpression results in enlarged hearts and increased activation of the kinase TOR. This enlarged heart phenotype can be rescued by inhibiting TOR signalling using rapamycin. They use RNA sequencing to identify genes that are dysregulated in HRASG12V hearts and are returned to nearly normal expression levels by rapamycin treatment. Over 2000 of these genes are similarly dysregulated in regenerating zebrafish hearts, suggesting that regeneration and oncogene-induced proliferation share some common pathways. Indeed, the authors find that transient expression of HRASG12V in hearts prior to injury results in increased cardiomyocyte dedifferentiation and proliferation, ultimately leading to a reduction in wound area without an increase in ventricle size. Overall, this work compares oncogene-induced proliferation and regeneration in the same model system to uncover similarities between these two processes.

The Company of Biologists

Development Jun 20, 2023

Non-canonical imprinting in the spotlight

Read this Spotlight by Julien Richard Albert & Maxim Greenberg on non-canonical imprinting, what is known about the conservation of this phenomenon & how it impacts mammalian development:

https://journals.biologists.com/dev/article/150/12/dev201087/316686/Non-canonical-imprinting-in-the-spotlight

Non-canonical imprinting in the spotlight

Summary: The latest findings on non-canonical imprinting and a discussion of what is known about the conservation of this phenomenon and how it impacts mammalian development.

The Company of Biologists

Development Jun 14, 2023

Issue 11 is now complete!

On the cover: mouse blastocysts were cultured and trophoectoderm was differentiated to highly polyploid trophoblast giant cells. See Singh et al.: https://journals.biologists.com/dev/article/150/11/dev201581/316006/Myc-promotes-polyploidy-in-murine-trophoblast

Also in Issue 11:
▪ 4 Research Highlights on cell trajectories, EHT, Myc & Notch
▪ Author interview with Yuki Sato
▪ 2 Spotlights on hPSCs maturation & the challenges studying early human development
▪ Meeting review on quantitative modelling workshop

https://journals.biologists.com/dev/issue/150/11

Myc promotes polyploidy in murine trophoblast cells and suppresses senescence

Highlighted Article: Polyploidy is widespread in murine placental cell types. The transcription factor MYC supports polyploidy and prevents premature senescence in trophoblast giant cells.

The Company of Biologists

Development Jun 6, 2023

Maturing differentiated human pluripotent stem cells in vitro: methods and challenges

A Spotlight by Daniele Ottaviani, Milena Bellin, Christine Mummery & colleagues, discussing the challenges of hPSC maturation in vitro, using cardiomyocytes as an example.

https://journals.biologists.com/dev/article/150/11/dev201103/310868/Maturing-differentiated-human-pluripotent-stem

Maturing differentiated human pluripotent stem cells in vitro: methods and challenges

Summary: A Spotlight on the challenges of maturing cells that are differentiated from human pluripotent stem cells in vitro, discussing methods to drive cardiomyocyte maturation, as an example.

The Company of Biologists

Development Jun 6, 2023

Calculating cell differentiation trajectories

Read this Research Highlight showcasing work from
Simon Freedman, Bingxian Xu, Sidhartha Goyal & Madhav Mani:

https://journals.biologists.com/dev/article/150/11/e150_e1101/312632/Calculating-cell-differentiation-trajectories

Read the full #OpenAccess Research Article 'A dynamical systems treatment of transcriptomic trajectories in hematopoiesis' here:

https://journals.biologists.com/dev/article/150/11/dev201280/312613/A-dynamical-systems-treatment-of-transcriptomic

Calculating cell differentiation trajectories

Cell differentiation during development is traditionally viewed as a series of bifurcations (points at which cells can adopt one of two distinct fates) underpinned by complex gene regulatory networks. In addition to this ‘Waddington landscape’ view of cell fate decisions, cells might undergo gradual changes in the expression of a multitude of genes as one cell type transitions into another. Now, Simon Freedman and colleagues employ a branch of mathematics known as dynamical systems to analyse cell fate decisions from published single-cell RNA sequencing (scRNA-seq) data of haematopoiesis. Using pseudotime as a control parameter for the dynamical system, the researchers identify two statistical signatures that represent one-to-one transitions and one-to-many cell fate bifurcations. By combining scRNA-seq data and a mathematical toy model, the authors can identify a cell fate decision bifurcation from a progenitor cell into the neutrophil lineage. Subsequently, they reveal one-to-one transitions during neutrophil development that reflect the linear maturation of the lineage into mature neutrophils. Finally, by focusing on specific parts of dynamical systems theory (eigenvectors), they can pinpoint bifurcations in scRNA-seq datasets. Together, this work helps to produce a predictive understanding of cellular trajectories of differentiation from scRNA-seq data.

The Company of Biologists

Development Jun 5, 2023

Issue 10 is now complete!

On the cover: newly differentiated fat bodies (green) with lipid droplets (magenta) in the abdomen of a pharate adult fly. See Research article by Tsuyama et al: https://journals.biologists.com/dev/article/150/10/dev200815/310416/Dynamic-de-novo-adipose-tissue-development-during

Also in Issue 10:
▪5 Research Highlights on DH31, Hoxb, Shrub, EIF4A3 & morphogen gradients
▪Juan Modolell Obituary
▪Author interview with Zainab Afzal & Robb Krumlauf
▪Brain development & neurodegeneration Spotlight
▪Human embryo implantation Review

https://journals.biologists.com/dev/issue/150/10

Dynamic de novo adipose tissue development during metamorphosis in Drosophila melanogaster

Summary: Drosophila adult fat body precursor cells form adult adipose tissue during metamorphosis by directional migration, continuous cell proliferation and homotypic cell fusion.

The Company of Biologists

Development Jun 2, 2023

Human embryo implantation

Read this #OpenAccess Review from Joanne Muter, Vincent Lynch, Rajiv McCoy,
Jan Brosens from the University of Warwick, examining the foundational processes of pregnancy from an evolutionary perspective:

https://journals.biologists.com/dev/article/150/10/dev201507/310869/Human-embryo-implantation

Human embryo implantation

Summary: This Review examines the foundational processes of pregnancy from an evolutionary perspective, highlights uterine remodelling permissive for implantation, and examines the impact of embryo fitness on endometrial homeostasis.

The Company of Biologists

Development Jun 2, 2023

Alex Eve Jun 1, 2023

I'm at #cshlsymp23! Happy to chat about @Dev_journal, @the_node and the @Co_Biologists charitable activities!

Development Jun 1, 2023

Of mice and men: a conserved role for EIF4A3 in neurogenesis

Read this Research Highlight showcasing work from Bianca Lupan, Rachel Solecki, Camila Musso, Fernando Alsina & Debra Silver from Duke University Medical Center:

https://journals.biologists.com/dev/article/150/10/e150_e1004/310766/Of-mice-and-men-a-conserved-role-for-EIF4A3-in

Read the Research Article 'The exon junction complex component EIF4A3 is essential for mouse and human cortical progenitor mitosis and neurogenesis' here:

https://journals.biologists.com/dev/article/150/10/dev201619/310754/The-exon-junction-complex-component-EIF4A3-is

Of mice and men: a conserved role for EIF4A3 in neurogenesis

Mutations in the exon junction complex (EJC) components can cause neurodevelopmental disorders, demonstrating a vital role for EJC-mediated RNA metabolism in brain development. Here, Debra Silver and colleagues uncover a key role for EIF4A3, a core EJC protein, in mediating neurogenesis in mouse and human neural progenitors. First, the authors observe extensive cell death and impaired brain development in Eif4a3 haploinsufficient mutant mice. Using live imaging, they find that mitosis of the progenitors in these mice is delayed, leading to more neuronal progeny and cell death. Previous studies have also observed links between mitosis duration and altered progenitor fate. To disentangle effects on cell fate and cell death, the authors look at Eif4a3;p53 compound mutant mice, and find that although most brain defects can be rescued by preventing p53-dependent apoptosis, there are additional p53-independent mechanisms through which EIF4A3 contributes to neurogenesis. Importantly, the authors observe that these progenitor defects are recapitulated in human pluripotent stem cell-derived organoids where EIF4A3 is mutated. Finally, the authors present evidence showing that EIF4A3 acts together with other EJC components to control progenitor function. Overall, this study provides new insights into the mechanisms of brain development, identifying a conserved role of EIF4A3 in mitosis, cell fate and the regulation of neural progenitors.

The Company of Biologists

Development May 31, 2023

Smaller cells make more precise patterns

Read this Research Highlight showcasing work from Jan A. Adelmann, Roman Vetter, and
Dagmar Iber:

https://journals.biologists.com/dev/article/150/10/e150_e1005/310835/Smaller-cells-make-more-precise-patterns

Read the full #OpenAcess Research Article 'The impact of cell size on morphogen gradient precision' here:

https://journals.biologists.com/dev/article/150/10/dev201702/310824/The-impact-of-cell-size-on-morphogen-gradient

Smaller cells make more precise patterns

Morphogen gradients play a crucial role in defining epithelial patterning during development. Despite variations in morphogen gradients, pattern readout is remarkably consistent across different embryos. Here, Dagmar Iber and colleagues extend their existing mathematical model of gradient variability to investigate the importance of cell size during patterning. They predict that reduced cell surface area in the developing epithelium should lead to increased gradient precision. Indeed, a literature search reveals that epithelial tissues patterned by morphogen gradients tend to exhibit smaller cell surface areas than tissues with no known morphogen gradient. The authors postulate that this apparent advantage of small cell surface areas could explain the evolution of pseudostratified epithelia. Their model also shows that the positional error is also affected by gradient decay length (with this error predicted to increase as the tissue grows) and by the size of the morphogen source. Using data from the developing Drosophila wing disc, they demonstrate that the effect of tissue growth can be buffered by an increase in morphogen source size and a decrease in epithelial cell surface area. Overall, this work provides new insight into how such precise patterning is achieved during development.

The Company of Biologists