Morphological scaling relationships, or allometries, describe how traits grow coordinately and covary among individuals in a population. The developmental regulation of scaling is essential to generate correctly proportioned adults across a range of body sizes, while the mis-regulation of scaling may result in congenital birth defects. Research over several decades has identified the developmental mechanisms that regulate the size of individual traits. Nevertheless, we still have poor understanding of how these mechanisms work together to generate correlated size variation among traits in response to environmental and genetic variation. Conceptually, morphological scaling can be generated by size-regulatory factors that act directly on multiple growing traits (trait-autonomous scaling), or indirectly via hormones produced by central endocrine organs (systemically regulated scaling), and there are a number of well-established examples of such mechanisms. There is much less evidence, however, that genetic and environmental variation actually acts on these mechanisms to generate morphological scaling in natural populations. More recent studies indicate that growing organs can themselves regulate the growth of other organs in the body. This suggests that covariation in trait size can be generated by network-regulated scaling mechanisms that respond to changes in the growth of individual traits. Testing this hypothesis, and one of the main challenges of understanding morphological scaling, requires connecting mechanisms elucidated in the laboratory with patterns of scaling observed in the natural world. This article is categorized under: Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Comparative Development and Evolution > Organ System Comparisons Between Species.
Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for investigating cell states and functions at the single-cell level. It has greatly revolutionized transcriptomic studies in many life science research fields, such as neurobiology, immunology, and developmental biology. With the fast development of both experimental platforms and bioinformatics approaches over the past decade, scRNA-seq is becoming economically feasible and experimentally practical for many biomedical laboratories.Drosophilahas served as an excellent model organism for dissecting cellular and molecular mechanisms that underlie tissue development, adult cell function, disease, and aging. The recent application of scRNA-seq methods toDrosophilatissues has led to a number of exciting discoveries. In this review, I will provide a summary of recent scRNA-seq studies inDrosophila, focusing on technical approaches and biological applications. I will also discuss current challenges and future opportunities of making new discoveries using scRNA-seq inDrosophila. This article is categorized under: Technologies > Analysis of the Transcriptome
Vertebrate nervous system function requires glial cells, including myelinating glia that insulate axons and provide trophic support that allows for efficient signal propagation by neurons. In vertebrate peripheral nervous systems, neural crest-derived glial cells known as Schwann cells (SCs) generate myelin by encompassing and iteratively wrapping membrane around single axon segments. SC gliogenesis and neurogenesis are intimately linked and governed by a complex molecular environment that shapes their developmental trajectory. Changes in this external milieu drive developing SCs through a series of distinct morphological and transcriptional stages from the neural crest to a variety of glial derivatives, including the myelinating sublineage. Cues originate from the extracellular matrix, adjacent axons, and the developing SC basal lamina to trigger intracellular signaling cascades and gene expression changes that specify stages and transitions in SC development. Here, we integrate the findings from in vitro neuron-glia co-culture experiments with in vivo studies investigating SC development, particularly in zebrafish and mouse, to highlight critical factors that specify SC fate. Ultimately, we connect classic biochemical and mutant studies with modern genetic and visualization tools that have elucidated the dynamics of SC development. This article is categorized under: Signaling Pathways > Cell Fate Signaling Nervous System Development > Vertebrates: Regional Development
Characterizing the proteome composition of organelles and subcellular regions of living cells can facilitate the understanding of cellular organization as well as protein interactome networks. Proximity labeling-based methods coupled with mass spectrometry (MS) offer a high-throughput approach for systematic analysis of spatially restricted proteomes. Proximity labeling utilizes enzymes that generate reactive radicals to covalently tag neighboring proteins. The tagged endogenous proteins can then be isolated for further analysis by MS. To analyze protein-protein interactions or identify components that localize to discrete subcellular compartments, spatial expression is achieved by fusing the enzyme to specific proteins or signal peptides that target to particular subcellular regions. Although these technologies have only been introduced recently, they have already provided deep insights into a wide range of biological processes. Here, we provide an updated description and comparison of proximity labeling methods, as well as their applications and improvements. As each method has its own unique features, the goal of this review is to describe how different proximity labeling methods can be used to answer different biological questions. This article is categorized under: Technologies > Analysis of Proteins.
The pulmonary system is comprised of two main compartments, airways and alveolar space. Their tissue and cellular complexity ensure lung function and protection from external agents, for example, virus. Two-dimensional (2D) in vitro systems and animal models have been largely employed to elucidate the molecular mechanisms underlying human lung development, physiology, and pathogenesis. However, neither of these models accurately recapitulate the human lung environment and cellular crosstalk. More recently, human-derived three-dimensional (3D) models have been generated allowing for a deeper understanding of cell-to-cell communication. However, the availability and accessibility of primary human cell sources from which generate the 2D and 3D models may be limited. In the past few years, protocols have been developed to successfully employ human pluripotent stem cells (hPSCs) and differentiate them toward pulmonary fate in vitro. In the present review, we discuss the advantages and pitfalls of hPSC-derived lung 2D and 3D models, including the main characteristics and potentials for these models and their current and future applications for modeling development and diseases. Lung organoids currently represent the closest model to the human pulmonary system. We further focus on the applications of lung organoids for the study of human diseases such as pulmonary fibrosis, infectious diseases, and lung cancer. Finally, we discuss the present limitations and potential future applications of 3D lung organoids. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion.
