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1. Anterior trunk muscle shows mix of axial and appendicular developmental patterns

   https://doi.org/10.1002/dvdy.95  

   Sagarin, Kathleen A.; Redgrave, Anna C.; Mosimann, Christian; Burke, Ann C.; Devoto, Stephen H. (January 2019, Developmental dynamics)

   null (Ed.)

   Background: Skeletal muscle in the trunk derives from the somites, paired segments of paraxial mesoderm. Whereas axial musculature develops within the somite, appendicular muscle develops following migration of muscle precursors into lateral plate mesoderm. The development of muscles bridging axial and appendicular systems appears mixed. Results: We examine development of three migratory muscle precursor-derived muscles in zebrafish: the sternohyoideus (SH), pectoral fin (PF), and posterior hypaxial (PHM) muscles. We show there is an anterior to posterior gradient to the developmental gene expression and maturation of these three muscles. SH muscle precursors exhibit a long delay between migration and differentiation, PF muscle precursors exhibit a moderate delay in differentiation, and PHM muscle precursors show virtually no delay between migration and differentiation. Using lineage tracing, we show that lateral plate contribution to the PHM muscle is minor, unlike its known extensive contribution to the PF muscle and absence in the ventral extension of axial musculature. Conclusions: We propose that PHM development is intermediate between a migratory muscle mode and an axial muscle mode of development, wherein the PHM differentiates after a very short migration of its precursors and becomes more anterior primarily by elongation of differentiated muscle fibers. 

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2. Directed Differentiation of Human Pluripotent Stem Cells to Podocytes under Defined Conditions

   https://doi.org/10.1038/s41598-019-39504-8  

   Qian, Tongcheng; Hernday, Shaenah E.; Bao, Xiaoping; Olson, William R.; Panzer, Sarah E.; Shusta, Eric V.; Palecek, Sean P. (February 2019, Scientific Reports)

   Abstract A major cause of chronic kidney disease (CKD) is glomerular disease, which can be attributed to a spectrum of podocyte disorders. Podocytes are non-proliferative, terminally differentiated cells. Thus, the limited supply of primary podocytes impedes CKD research. Differentiation of human pluripotent stem cells (hPSCs) into podocytes has the potential to produce podocytes for disease modeling, drug screening, and cell therapies. In the podocyte differentiation process described here, hPSCs are first induced to primitive streak-like cells by activating canonical Wnt signaling. Next, these cells progress to mesoderm precursors, proliferative nephron progenitors, and eventually become mature podocytes by culturing in a serum-free medium. Podocytes generated via this protocol adopt podocyte morphology, express canonical podocyte markers, and exhibit podocyte phenotypes, including albumin uptake and TGF-β1 triggered cell death. This study provides a simple, defined strategy to generate podocytes forin vitromodeling of podocyte development and disease or for cell therapies. 

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3. Altering metabolite distribution at Xenopus cleavage stages affects left–right gene expression asymmetries

   https://doi.org/10.1002/dvg.23418  

   Onjiko, Rosemary M.; Nemes, Peter; Moody, Sally A. (April 2021, genesis)

   Summary The left–right (L–R) axis of most bilateral animals is established during gastrulation when a transient ciliated structure creates a directional flow of signaling molecules that establish asymmetric gene expression in the lateral plate mesoderm. However, in some animals, an earlier differential distribution of molecules and cell division patterns initiate or at least influence L–R patterning. Using single‐cell high‐resolution mass spectrometry, we previously reported a limited number of small molecule (metabolite) concentration differences between left and right dorsal‐animal blastomeres of the eight‐cellXenopusembryo. Herein, we examined whether altering the distribution of some of these molecules influenced early events in L–R patterning. Using lineage tracing, we found that injecting right‐enriched metabolites into the left cell caused its descendant cells to disperse in patterns that varied from those in control gastrulae; this did not occur when left‐enriched metabolites were injected into the right cell. At later stages, injecting left‐enriched metabolites into the right cell perturbed the expression of genes known to: (a) be required for the formation of the gastrocoel roof plate (foxj1); (b) lead to the asymmetric expression of Nodal (dand5/coco); or (c) result from asymmetricalnodalexpression (pitx2). Despite these perturbations in gene expression, we did not observe heterotaxy in heart or gut looping at tadpole stages. These studies indicate that altering metabolite distribution at cleavage stages at the concentrations tested in this study impacts the earliest steps of L–R gene expression that then can be compensated for during organogenesis. 

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4. The non-canonical Wnt receptor Ror2 is required for cartilage cell polarity and morphogenesis of the craniofacial skeleton in zebrafish

   https://doi.org/10.1242/dev.201273  

   Dranow, Daniel B.; Le Pabic, Pierre; Schilling, Thomas F. (April 2023, Development)

   ABSTRACT Non-canonical/β-catenin-independent Wnt signaling plays crucial roles in tissue/cell polarity in epithelia, but its functions have been less well studied in mesenchymal tissues, such as the skeleton. Mutations in non-canonical Wnt signaling pathway genes cause human skeletal diseases such as Robinow syndrome and Brachydactyly Type B1, which disrupt bone growth throughout the endochondral skeleton. Ror2 is one of several non-canonical Wnt receptor/co-receptors. Here, we show that ror2−/− mutant zebrafish have craniofacial skeletal defects, including disruptions of chondrocyte polarity. ror1−/− mutants appear to be phenotypically wild type, but loss of both ror1 and ror2 leads to more severe cartilage defects, indicating partial redundancy. Skeletal defects in ror1/2 double mutants resemble those of wnt5b−/− mutants, suggesting that Wnt5b is the primary Ror ligand in zebrafish. Surprisingly, the proline-rich domain of Ror2, but not its kinase domain, is required to rescue its function in mosaic transgenic experiments in ror2−/− mutants. These results suggest that endochondral bone defects in ROR-related human syndromes reflect defects in cartilage polarity and morphogenesis. 

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5. Vascular Smooth Muscle Cell Subpopulations and Neointimal Formation in Mouse Models of Elastin Insufficiency

   https://doi.org/10.1161/ATVBAHA.120.315681  

   Lin, Chien-Jung; Hunkins, Bridget M.; Roth, Robyn A.; Lin, Chieh-Yu; Wagenseil, Jessica E.; Mecham, Robert P. (December 2021, Arteriosclerosis, Thrombosis, and Vascular Biology)

   Objective: Using a mouse model of Eln (elastin) insufficiency that spontaneously develops neointima in the ascending aorta, we sought to understand the origin and phenotypic heterogeneity of smooth muscle cells (SMCs) contributing to intimal hyperplasia. We were also interested in exploring how vascular cells adapt to the absence of Eln. Approach and Results: We used single-cell sequencing together with lineage-specific cell labeling to identify neointimal cell populations in a noninjury, genetic model of neointimal formation. Inactivating Eln production in vascular SMCs results in rapid intimal hyperplasia around breaks in the ascending aorta’s internal elastic lamina. Using lineage-specific Cre drivers to both lineage mark and inactivate Eln expression in the secondary heart field and neural crest aortic SMCs, we found that cells with a secondary heart field lineage are significant contributors to neointima formation. We also identified a small population of secondary heart field-derived SMCs underneath and adjacent to the internal elastic lamina. Within the neointima of SMC-Eln knockout mice, 2 unique SMC populations were identified that are transcriptionally different from other SMCs. While these cells had a distinct gene signature, they expressed several genes identified in other studies of neointimal lesions, suggesting that some mechanisms underlying neointima formation in Eln insufficiency are shared with adult vessel injury models. Conclusions: These results highlight the unique developmental origin and transcriptional signature of cells contributing to neointima in the ascending aorta. Our findings also show that the absence of Eln, or changes in elastic fiber integrity, influences the SMC biological niche in ways that lead to altered cell phenotypes. 

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