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1. Putting in the Erk: Growth factor signaling and mesoderm morphogenesis

   https://doi.org/10.1016/bs.ctdb.2022.02.007  

   McFann, Sarah E.; Shvartsman, Stanislav Y.; Toettcher, Jared E. (January 2022, Current Topics in Developmental Biology)

   Soriano, Phillippe M. (Ed.)

   It has long been known that FGF signaling contributes to mesoderm formation, a germ layer found in triploblasts that is composed of highly migratory cells that give rise to muscles and to the skeletal structures of vertebrates. FGF signaling activates several pathways in the developing mesoderm, including transient activation of the Erk pathway, which triggers mesodermal fate specification through the induction of the gene brachyury and activates morphogenetic programs that allow mesodermal cells to position themselves in the embryo. In this review, we discuss what is known about the generation and interpretation of transient Erk signaling in mesodermal tissues across species. We focus specifically on mechanisms that translate the level and duration of Erk signaling into cell fate and cell movement instructions and discuss strategies for further interrogating the role that Erk signaling dynamics play in mesodermal gastrulation and morphogenesis. 

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2. Variations in Tissue Interactions During Head Muscle Development

   https://doi.org/10.1002/ar.25522  

   Ziermann-Canabarro, Janine M; Correa-Alfonzo, Paola (June 2024, The Anatomical Record)

   For decades it has been established that head muscle development differs from trunk muscle development. Similarly known, even though not in such detail, is that different subgroups of head muscles develop dependent on different underlying gene regulatory networks. Even less well studied are the tissue interactions during the developmental processes. Muscles derived from pharyngeal arch mesoderm depend on interactions with endoderm and neural crest cells, and, to a minor extent, ectodermal cues. Extraocular eye muscles respond to a mix of signals from surrounding mesoderm, but also neural crest cells; however, they are independent of endodermal cues. Head muscles derived from occipital paraxial mesoderm depend on tissue interactions similar to pharyngeal arch muscles but have a different migration trajectory. While the pharyngeal arch mesodermal cells and neural crest cells largely migrate from dorsal to ventral, the occipital paraxial mesodermal cells migrate from dorsal to ventral and from posterior to anterior. During the migration these cells proliferate and even start to differentiate, while pharyngeal mesodermal cells begin the differentiation process after reaching their respective pharyngeal arches. Here we present an overview of tissue interactions during the development of different head muscle populations, highlighting general concepts and main differences. Topic Category: Neural Crest, Placodes and Craniofacial Development Keywords: Craniofacial muscles, Myogenesis Funding or Support Information: NSF #2000005 to JMZC 

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3. Developmental single-cell transcriptomics in the Lytechinus variegatus sea urchin embryo

   https://doi.org/10.1242/dev.198614  

   Massri, Abdull J.; Greenstreet, Laura; Afanassiev, Anton; Berrio, Alejandro; Wray, Gregory A.; Schiebinger, Geoffrey; McClay, David R. (October 2021, Development)

   ABSTRACT Using scRNA-seq coupled with computational approaches, we studied transcriptional changes in cell states of sea urchin embryos during development to the larval stage. Eighteen closely spaced time points were taken during the first 24 h of development of Lytechinus variegatus (Lv). Developmental trajectories were constructed using Waddington-OT, a computational approach to ‘stitch’ together developmental time points. Skeletogenic and primordial germ cell trajectories diverged early in cleavage. Ectodermal progenitors were distinct from other lineages by the 6th cleavage, although a small percentage of ectoderm cells briefly co-expressed endoderm markers that indicated an early ecto-endoderm cell state, likely in cells originating from the equatorial region of the egg. Endomesoderm cells also originated at the 6th cleavage and this state persisted for more than two cleavages, then diverged into distinct endoderm and mesoderm fates asynchronously, with some cells retaining an intermediate specification status until gastrulation. Seventy-nine out of 80 genes (99%) examined, and included in published developmental gene regulatory networks (dGRNs), are present in the Lv-scRNA-seq dataset and are expressed in the correct lineages in which the dGRN circuits operate. 

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4. Control of gastruloid patterning and morphogenesis by the Erk and Akt signaling pathways

   https://doi.org/10.1242/dev.201663  

   Underhill, Evan J.; Toettcher, Jared E. (August 2023, Development)

   ABSTRACT Many developmental processes rely on the localized activation of receptor tyrosine kinases and their canonical downstream effectors Erk and Akt, yet the specific roles played by each of these signals is still poorly understood. Gastruloids, 3D cell culture models of mammalian gastrulation and axial elongation, enable quantitative dissection of signaling patterns and cell responses in a simplified, experimentally accessible context. We find that mouse gastruloids contain posterior-to-anterior gradients of Erk and Akt phosphorylation induced by distinct receptor tyrosine kinases, with features of the Erk pattern and expression of its downstream target Snail exhibiting hallmarks of size-invariant scaling. Both Erk and Akt signaling contribute to cell proliferation, whereas Erk activation is also sufficient to induce Snail expression and precipitate profound tissue shape changes. We further uncover that Erk signaling is sufficient to convert the entire gastruloid to one of two mesodermal fates depending on position along the anteroposterior axis. In all, these data demonstrate functional roles for two core signaling gradients in mammalian development and suggest how these modules might be harnessed to engineer user-defined tissues with predictable shapes and cell fates. 

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5. Quantitative Analysis of Transcriptome Dynamics Provides Novel Insights into Developmental State Transitions

   https://doi.org/10.1101/2022.03.10.483850  

   Johnson, Kristin; Freedman, Simon; Braun, Rosemary; LaBonne, Carole (March 2022, bioRxiv)

   During embryogenesis, the developmental potential of initially pluripotent cells becomes progressively restricted as they transit to lineage restricted states. The pluripotent cells of Xenopus blastula-stage embryos are an ideal system in which to study cell state transitions during developmental decision-making, as gene expression dynamics can be followed at high temporal resolution. Here we use transcriptomics to interrogate the process by which pluripotent cells transit to four different lineage-restricted states: neural progenitors, epidermis, endoderm and ventral mesoderm, providing quantitative insights into the dynamics of Waddington’s landscape. Our findings shed light on why the neural progenitor state is the default lineage state for pluripotent cells, and uncover novel components of lineage-specific gene regulation. These data reveal an unexpected overlap in the transcriptional responses to BMP4/7 and activin signaling, and provide mechanistic insight into how the timing of signaling inputs such as BMP are temporally controlled to ensure correct lineage decisions. Together these analyses provide quantitative insights into the logic and dynamics of developmental decision making in early embryos. 

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