Developmental Biology

eLife assessment

The authors present an exciting idea about how to integrate morphogens into a gene regulatory network with the dynamics of morphogenesis and cell movement. It represents a novel methodology, but in its current form the hypotheses, data and relationships described do not provide a sufficiently compelling model to disentangle cause and effect or elucidate the impact of cell movements on differentiation dynamics the zebrafish mesoderm.

Evaluation Summary

This manuscript demonstrates that male mice lacking androglobin, a poorly understood heme-containing protein, are infertile and have defects in late stage spermatogenesis. A variety of molecular techniques were used to delineate the mechanism of spermatogenesis defect. A strength of the data is the identification of the androglobin interacting partner septin 10. With some clearer data on the mechanism underlying the connection between androglobin and septin, the paper will be of interest to researchers studying spermatogenesis.

(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.)

Evaluation Summary:

In this paper, Bostock and Fernandes show that photoreceptor axons provide a graded Hedgehog signal to their target region, the lamina, that is highest in the distal and lowest in the proximal lamina. High levels of Hh favor specification of the distally located lamina neurons L2 and L3, while low levels favor specification of the proximal L5 neurons. This graded response raises interesting parallels with the patterning of the vertebrate spinal cord. The paper will be of special interest to those who study optic lobe development, but will also be of more general interest to developmental neurobiology.

This manuscript was co-submitted with: https://www.biorxiv.org/content/10.1101/2021.12.13.472383v2

(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.)

Evaluation Summary:

The results in this report are intriguing in providing evidence that differences in codon optimality in mRNAs can underlie tissue-specific differences in expression and that this phenomenon operates in restricting expression of an evolutionarily young endogenous genes to the testis versus ovaries in a manner important for female fertility in the fruit fly. The scientific quality of the work would be further enhanced by additional experiments to determine whether the differences in expression arise primarily at the translational level or also/rather involve altered mRNA turnover or transcription in response to poor codon usage outside of testis and brain.

(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 #2 agreed to share their name with the authors.)

Evaluation Summary:

This paper will be of broad interest to scientists who study collective cell migration and cytoskeletal dynamics. The findings of this paper connect proteins involved in planar polarity to the actin protrusive machinery which establishes an axes for polarized collective cell migration. The data presented largely supports the claims of the authors who take advantage of quantitative imaging techniques and Drosophila genetics to establish this connection.

(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.)

Evaluation Summary:

This paper will be of interest to lung biologists, developmental biologists, and neonatologists interested in lung injury. In this manuscript, the authors used gene expression signatures to construct a gene regulatory network to identify genes associated with alveologenesis. While reviewers were impressed with the novelty of the approach, questions were raised about the robustness of the results in mice and the validation in human samples.

(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.)

Evaluation Summary:

Hoye et al. analyzed conditional inactivation of Ddx3x gene in mouse dorsal forebrain, which leads to decreased brain size and widespread apoptosis in females but not males. Interestingly, the authors showed that Ddx3y was transcriptionally upregulated in cKO males, and suggested that Ddx3y compensated for the loss of Ddx3x. These results are attributed to prolonged cell cycle, impaired cell cycle exit, leading to increased progenitor populations. Ribo-Seq analysis showed differentially translated genes, providing potential new insights into Ddx3x function and pathogenic mechanisms. Overall, this study is of great importance and provides novel insights into the pathogenesis of DDX3X syndrome and the crucial role of DDX3X during cortical 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.)

Evaluation Summary:

This paper puts forward a new approach to generate vascularized brain organoids to copy in vivo structures, which will be of interest to neurobiologists working in both basic and disease-related areas of neuroscience. The novelty of their approach lies in the simultaneous production of vessel-like networks and brain-resident microglia immune cells in a single organoid. The fusion of brain and vessel organoids (fVBOrs) resulted in robust engraftment of vessel-like structures and microglia around ventricular zone (VZ)-like structures, correlating with increased neuronal progenitors. The conclusions are mostly well supported by the data, but a few points need to be clarified and some conclusions would benefit from further experimental support.

(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.)

Evaluation Summary:

This manuscript will be of interest to scientists working on genome organisation and transcriptional control of myelination during mammalian brain development. The authors combine diverse and complimentary experimental approaches to generate insights into how DNA looping contributes to transcriptional regulation in functionally specialised cell types. The experiments have been rigorously performed and the main conclusions are justified.

(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.)

Evaluation Summary:

This study employs cutting-edge, multiview light-sheet microscopy and advanced image analysis to investigate how the mechanical interplay of two adjacent tissue layers shapes a developing organ. The finding that genetically-patterned calcium pulses induce local muscle contractions that constrict and fold the adjacent endoderm offers a novel mechanism by which genetically encoded patterning information shapes organs across tissue layers.

(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.)