Developmental Biology

Asynchronous mouse embryo polarization leads to heterogeneity in cell fate specification

1. Adiyant Lamba
2. Meng Zhu
3. Maciej Meglicki
4. Sylwia Czukiewska
5. Lakshmi Balasubramaniam
6. Ron Hadas
7. Nina Weishaupt
8. Ekta M Patel
9. Yu Hua Kavanagh
10. Ran Wang
11. Naihe Jing
12. Magdalena Zernicka-Goetz

• Curated by eLife

  eLife Assessment

  This fundamental work substantially advances our understanding of the molecular basis by which early symmetry breaking events connect to the following cell fate specifications in preimplantation mammalian embryos. The evidence supporting the conclusions is compelling, with advanced image based assays and microinjection based functional tests. The work will be of broad interest to cell and developmental biologists.

Reviewed by eLife

Dissecting infant leukemia developmental origins with a hemogenic gastruloid model

1. Denise Ragusa
2. Chun Wai Suen
3. Gabriel Torregrosa Cortes
4. Fabio Pastorino
5. Ayona Johns
6. Ylenia Cicirò
7. Liza Dijkhuis
8. Susanne van den Brink
9. Michele Cilli
10. Connor Byrne
11. Giulia-Andreea Ionescu
12. Joana Cerveira
13. Kamil R Kranc
14. Victor Hernandez-Hernandez
15. Mirco Ponzoni
16. Anna Bigas
17. Jordi Garcia-Ojalvo
18. Alfonso Martínez Arias
19. Cristina Pina

• Curated by eLife

  eLife Assessment

  This valuable study presents a mouse gastruloid system to generate successive waves of hematopoietic progenitors that in vivo would emerge during embryonic development. Although this newly revised manuscript has addressed some of the concerns raised during the first round of review, the study is still considered incomplete, as the claims are only partially supported. In particular, the claim of definitive wave hematopoietic progenitors being produced in the gastruloids, and their engraftment after transplantation, would benefit from further validation.

Reviewed by eLife

Comprehensive profiling of migratory primordial germ cells reveals niche-specific differences in non-canonical Wnt and Nodal-Lefty signaling in anterior vs posterior migrants

1. Rebecca Garrett Jaszczak
2. Jay W Zussman
3. Daniel E Wagner
4. Diana J Laird

• Curated by eLife

  eLife Assessment

  This revised study provides fundamental insights into the differences in migratory primordial germ cells based on their anterior or posterior location. Through convincing methodology and analysis of single-cell RNA sequencing of an exceptionally large number of migratory primordial germ cells and surrounding somatic cells, the novel findings and datasets generated from this study provide many hypotheses of interest to germ cell biologists.

Reviewed by eLife

TET knockout cells transit between pluripotent states and exhibit precocious germline entry

1. Raphaël Pantier
2. Elisa Barbieri
3. Sara Gonzalez Brito
4. Ella Thomson
5. Tülin Tatar
6. Douglas Colby
7. Man Zhang
8. Ian Chambers

Reviewed by preLights

Massively parallel reporter assay for mapping gene-specific regulatory regions at single nucleotide resolution

1. Alastair J Tulloch
2. Ryan N Delgado
3. Rinaldo Catta-Preta
4. Constance L Cepko

• Curated by eLife

  eLife Assessment

  This manuscript presents a valuable methodological approach for investigating context-dependent activity of cis-regulatory elements within defined genomic loci. The authors combine a locus-specific massively parallel reporter assay, enabling unbiased and high-coverage profiling of enhancer activity across large genomic regions, with a degenerate reporter assay to identify nucleotides critical for enhancer function. The data supporting the conclusions are solid, highlighted by the successful identification and characterization of both previously known and new regulatory elements across multiple developmental stages, cell types, and species; however, concerns regarding assay sensitivity, statistical rigor in distinguishing active regions, and limitations inherent to the design of the reporter assays remain to be addressed. With strengthened quantitative analysis, statistical validation, and additional functional experiments to directly establish regulatory element-gene relationships, this study will be of broad interest to researchers investigating gene regulation mechanisms in development and disease.

Reviewed by eLife

Superoxide Dismutases maintain niche homeostasis in stem cell populations

1. Olivia Majhi
2. Aishwarya Chhatre
3. Tanvi Chaudhary
4. Devanjan Sinha

• Curated by eLife

  eLife Assessment

  In this work, the authors intend to assess the existence of a redox potential across germline stem cells and neighboring somatic stem cells in the Drosophila testis. Some aspects of the manuscript are solid, like the clear effect of SOD KD on cyst cell differentiation state. Other conclusions of the work, such as the non-autonomous effect of this KD in germ cells are not sufficiently supported by the data. The work is potentially useful if the critiques of the reviewers are fully addressed; the strength of the evidence of the manuscript as it stands is incomplete.

Reviewed by eLife

Synergistic and independent roles for Nodal and FGF in zebrafish cardiac progenitor cell migration and asymmetric heart morphogenesis

1. Vanessa Gonzalez
2. Meagan G. Grant
3. Makoto Suzuki
4. Briana Christophers
5. Jessica Rowland Williams
6. Rebecca D. Burdine

Reviewed by preLights

The microtubule-binding protein EML3 is required for mammalian embryonic growth and cerebral cortical development; Eml3 null mice are a model of cobblestone brain malformation

1. Isabelle Carrier
2. Eduardo Diez
3. Valerio EC Piscopo
4. Susanne Bechstedt
5. Hans van Bokhoven
6. Myriam Srour
7. Albert Berghuis
8. Stefano Stifani
9. Yojiro Yamanaka
10. Roderick R McInnes

• Curated by eLife

  eLife Assessment

  This important study is the first characterization of the phenotype caused by a lack of Eml3 expression in mice. Mutant animals present a disrupted pial basement membrane, leading to focal extrusions from the cerebral cortex, called ectopias. The methodology is convincing and the conclusions are solid, although further investigations on the mechanisms and inclusion of the experiments performed, but not presented, will improve the manuscript. This work would be of interest to neural development biologists and human geneticists working on brain disorders.

Reviewed by eLife

Gene regulatory mechanisms guiding bifurcation of inhibitory and excitatory neuron lineages in the mouse anterior brainstem

1. Sami Kilpinen
2. Lassi Virtanen
3. Silvana Bodington Celma
4. Amos Bonsdorff
5. Heidi Heliölä
6. Kaia Achim
7. Juha Partanen

• Curated by eLife

  eLife Assessment

  This work is a important resource for hypothesis testing of candidate upstream transcriptional regulatory factors that control the spatiotemporal expression of selector genes and their targets for GABAergic vs glutamatergic neuron fate in the anterior brainstem. Extensive high-quality datasets were generated and state of the art computational methods were convincingly implemented to identify candidate regulatory elements. The work will be of interest to biologists working to understand neuronal gene regulatory networks.

Reviewed by eLife

In vivo CRISPR screening identifies regulators of hyperplastic and hypertrophic adipose remodelling in zebrafish

1. Rebecca Wafer
2. Panna Tandon
3. James EN Minchin

• Curated by eLife

  eLife Assessment

  This is a well-written study that presents a solid genetic screen to identify regulators of adipose morphology and remodeling in zebrafish. The authors generated a rigorous screening platform based on live, whole animal imaging and statistical methods that revealed both novel and known genes critical for adipose regulation. This work is valuable because it provides several candidate genes relevant to metabolic health and a quantitative screening pipeline that will be beneficial for future studies. A limitation of the study is that it precludes a definitive distinction between developmental and remodeling effects.

Reviewed by eLife