Developmental Biology

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

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

Single-nucleus transcriptional and chromatin accessibility analyses of maturing mouse Achilles tendon uncover the molecular landscape of tendon stem/progenitor cells

1. Hiroki Tsutsumi
2. Tomoki Chiba
3. Yuta Fujii
4. Takahide Matsushima
5. Tsuyoshi Kimura
6. Akinori Kanai
7. Akio Kishida
8. Yutaka Suzuki
9. Hiroshi Asahara

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding of novel markers that may potentially identify resident tendon stem/progenitor cells (TSPCs). The study also presents a comprehensive single-cell transcriptional dataset that will be of value to the field. The evidence supporting the identification of novel markers of a TSPC is incomplete, requiring clarification of current analyses and additional validation experiments to demonstrate that these markers are indeed specific and these cells are indeed TSPCs. This work will be of interest to biologists and engineers focused on tendons and ligaments.

Reviewed by eLife

Molecular and mechanical signatures contributing to mouse epidermal differentiation and barrier formation

1. Alexandra Prado-Mantilla
2. Wenxiu Ning
3. Terry Lechler

• Curated by eLife

  eLife Assessment

  The authors address a fundamental question for cell and tissue biology. They use the skin epidermis as a paradigm and ask how stratifying self-renewing epithelia induce differentiation and upward migration in basal dividing progenitor cells to generate suprabasal barrier-forming cells that are essential for a functional barrier formed by such an epithelium. The authors provide compelling evidence time that an increase in intracellular actomyosin contractility, a hallmark of barrier-forming keratinocytes, is sufficient to trigger terminal differentiation, providing in vivo evidence of the interdependency of cell mechanics and differentiation. To illustrate their points, the authors use a combination of genetic mouse models, RNA sequencing, and immunofluorescence analysis. Precisely how the changes in gene expression, cell morphology, mechanics, and cell position are instructive and whether consecutive changes in differentiation are required still remain unclear, but the paper takes a nice step in advancing our knowledge of the process.

Reviewed by eLife

SoxB1 family members inhibit Wnt signaling to promote maturation and deposition of stable neuromasts by the zebrafish Posterior Lateral Line primordium

1. Greg Palardy
2. Kyeong-won Yoo
3. Sana Fatma
4. Abhishek Mukherjee
5. Chongmin Wang
6. Priyanka Ravi
7. Ajay B Chitnis

• Curated by eLife

  eLife Assessment

  This important study explores the regulation of collective cell migration and tissue patterning in the zebrafish posterior lateral line primordium by SoxB1 transcription factors. The authors provide evidence that SoxB1 genes interact with Wnt and Fgf signaling pathways to control neuromast deposition and spacing, a process central to sensory organ development. The work offers mechanistic insight into the self-organization of migrating tissues and adds to the understanding of how transcriptional networks integrate with signaling pathways during morphogenesis. However, the strength of the evidence supporting several key conclusions is incomplete due to insufficient validation of mutant and knockdown tools, lack of quantitative analysis, and unclear experimental design details; additional quantification and more rigorous verification of gene knockdown or loss-of-function tools are needed to support the proposed model.

Reviewed by eLife