Developmental Biology

Inhibition of β1-AR/Gαs signaling promotes cardiomyocyte proliferation in juvenile mice through activation of RhoA-YAP axis

1. Masahide Sakabe
2. Michael Thompson
3. Nong Chen
4. Mark Verba
5. Aishlin Hassan
6. Richard Lu
7. Mei Xin

• Curated by eLife

  Evaluation Summary:

  The authors identify a novel developmental role for the beta-adrenergic system in the regulation of mammalian cardiac regenerative capacity. Using genetic and pharmacological loss-of-function approaches, the authors identify a link between Yap and β-adrenergic receptor blockade. The conditional genetic loss-of-function studies are a particular strength of the manuscript and provide strong support for the Gas/Yap-dependent nature of the cardiomyocyte proliferative response to beta adrenergic blockade. Given the widespread use of beta blockers in the clinical management of heart failure, the findings are potentially very important. However, further evidence is required to substantiate the induction of bona fide cardiomyocyte proliferation and cardiac regeneration and clarify the associated mechanisms.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

miRNA-27a is essential for bone remodeling by modulating p62-mediated osteoclast signaling

1. Shumin Wang
2. Eri O Maruyama
3. John Martinez
4. Justin Lopes
5. Trunee Hsu
6. Wencheng Wu
7. Wei Hsu
8. Takamitsu Maruyama

• Curated by eLife

  Evaluation Summary:

  The authors show that MiR-27a affects osteoclast-mediated bone resorption but not osteoblast-mediated bone formation during skeletal remodeling. Through gene profiling and bioinformatics study authors also identify the specific target of miR-27a in the osteoclast gene. MiR-27a exerts its effects on osteoclast differentiation through modulation of P62. This paper is of interest to scientists within the field of bone biology. The manuscript data analysis and conclusion are clear and directly supporting the previous known findings.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Generation of a transparent killifish line through multiplex CRISPR/Cas9mediated gene inactivation

1. Johannes Krug
2. Birgit Perner
3. Carolin Albertz
4. Hanna Mörl
5. Vera L Hopfenmüller
6. Christoph Englert

• Curated by eLife

  Evaluation Summary:

  This study by Krug et al. uses the turquoise killifish, an emerging model for biomedical research, to generate a valuable live-imaging platform. Initially, the authors generate a transparent killifish they named Klara. Specifically, using optimized CRISPR approaches, they simultaneously inactivate three genes that are required for the formation of primary pigment cells in fish (melanophores, iridophores, xanthophores) and next, to monitor cell-cycle arrest and cellular senescence, they generate a cdkn1a-GFP reporter line using HDR-mediated integration. The paper would benefit from a further description of the HDR approach, the genetic models, and improved figures. Together, this platform will be an extremely valuable resource with broad application, including for aging research, physiology, toxicology, and regeneration.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

A human mitofusin 2 mutation can cause mitophagic cardiomyopathy

1. Antonietta Franco
2. Jiajia Li
3. Daniel P Kelly
4. Ray E Hershberger
5. Ali J Marian
6. Renate M Lewis
7. Moshi Song
8. Xiawei Dang
9. Alina D Schmidt
10. Mary E Mathyer
11. John R Edwards
12. Cristina de Guzman Strong
13. Gerald W Dorn

• Curated by eLife

  eLife assessment

  In this paper, the authors demonstrate an interesting link between mitofusin function (MFN2) and PARKIN recruitment and mitophagy, underlying cardiomyopathy. This is a valuable finding with broad implications for understanding the mitochondrial biology as well as mechanisms involved in heart pathologies. However, the analyses are incomplete and the main conclusions are only partially supported and need to be further evidenced.

Reviewed by eLife

Sex-specific role of myostatin signaling in neonatal muscle growth, denervation atrophy, and neuromuscular contractures

1. Marianne E Emmert
2. Parul Aggarwal
3. Kritton Shay-Winkler
4. Se-Jin Lee
5. Qingnian Goh
6. Roger Cornwall

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to scientists within the field of neuromuscular disorders and has potential clinical relevance. It reveals a novel targeted strategy to improve the pathophysiology of children with neonatal brachial plexus injury. The key claims of the manuscript are well supported by the data, and the approaches used are thoughtful and rigorous.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

The centrosomal protein 83 (CEP83) regulates human pluripotent stem cell differentiation toward the kidney lineage

1. Fatma Mansour
2. Christian Hinze
3. Narasimha Swamy Telugu
4. Jelena Kresoja
5. Iman B Shaheed
6. Christian Mosimann
7. Sebastian Diecke
8. Kai M Schmidt-Ott

• Curated by eLife

  Evaluation Summary:

  This work will be of interest to the field of researchers that generate human stem cell-derived kidney organoids to model genetic kidney diseases. It describes a novel and crucial role of the protein CEP83 in mesoderm patterning, which further determines whether kidney tissues can form correctly. Using cutting-edge technologies the authors provide strong data, which support the key claims of this manuscript. This work is of high impact due to the relevance of CEP83 mutations in human kidney disease.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Ectodermal Wnt signaling, cell fate determination, and polarity of the skate gill arch skeleton

1. Jenaid M Rees
2. Victoria A Sleight
3. Stephen J Clark
4. Tetsuya Nakamura
5. J Andrew Gillis

• Curated by eLife

  Evaluation Summary:

  In this highly innovative study, the authors use combinatorial gene expression analysis to study the development of the gill arch of the little skate. This process depends on Shh and Fgf ligand-derived endodermal cells at the endoderm-ectoderm junction, providing insight into not only the fundamental developmental mechanisms regulating brachial arch formation in cartilaginous fishes, but also highlighting a unique relationship between inhibition of Wnt and Hedgehog signaling pathways in the context of early appendage development. The work will be of interest to developmental biologists and colleagues studying Wnt and Hedgehog signaling pathways.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Combined lineage tracing and scRNA-seq reveals unexpected first heart field predominance of human iPSC differentiation

1. Francisco X Galdos
2. Carissa Lee
3. Soah Lee
4. Sharon Paige
5. William Goodyer
6. Sidra Xu
7. Tahmina Samad
8. Gabriela V Escobar
9. Adrija Darsha
10. Aimee Beck
11. Rasmus O Bak
12. Matthew H Porteus
13. Sean M Wu

• Curated by eLife

  Evaluation Summary:

  The derivation of cardiomyocytes from the first and second heart fields is a well-studied phenomenon in animal models, however, due to ethical concerns, has not been studied in human heart development. The authors utilize hiPSC technology to demonstrate that it is the FHF and SHF that give rise to cardiomyocytes which is an important step in furthering our understanding of early human heart development.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Lineage-specific differences and regulatory networks governing human chondrocyte development

1. Daniel Richard
2. Steven Pregizer
3. Divya Venkatasubramanian
4. Rosanne M Raftery
5. Pushpanathan Muthuirulan
6. Zun Liu
7. Terence D Capellini
8. April M Craft

• Curated by eLife

  Evaluation Summary:

  The study presented in this manuscript is of interest to cartilage biologists studying the mechanisms of chondrocyte differentiation. The authors investigated transcriptomic profiles of hESC-derived articular and growth plate chondrocytes. To characterize the regulatory landscapes with respective transcriptomes, they mapped chromatin accessibility in hESC derived chondrocyte lineages and mouse embryonic chondrocytes using ATAC-sequencing and revealed lineage-specific gene regulatory networks. They further validated functional interactions of two transcription factors, Runx2 and RELA, with their predicted genomic targets. This study could help us understand chondrocyte differentiation.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

DOT1L activity affects cell lineage progression in the developing brain by controlling metabolic programs

1. Bismark Appiah
2. Camilla L. Fullio
3. Christiane Haffner
4. Patrice Zeis
5. Martin Treppner
6. Patrick Bovio
7. Arquimedes Cheffer
8. Ilaria Bertani
9. Harald Binder
10. Dominic Grün
11. Nereo Kalebic
12. Elena Taverna
13. Tanja Vogel

Reviewed by Review Commons, preLights