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- Comai, Glenda Evangelina, et al.
(författare)
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Local retinoic acid signaling directs emergence of the extraocular muscle functional unit
- 2020
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Ingår i: PLoS biology. - : Public Library Science. - 1544-9173 .- 1545-7885. ; 18:11
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Tidskriftsartikel (refereegranskat)abstract
- Coordinated development of muscles, tendons, and their attachment sites ensures emergence of functional musculoskeletal units that are adapted to diverse anatomical demands among different species. How these different tissues are patterned and functionally assembled during embryogenesis is poorly understood. Here, we investigated the morphogenesis of extraocular muscles (EOMs), an evolutionary conserved cranial muscle group that is crucial for the coordinated movement of the eyeballs and for visual acuity. By means of lineage analysis, we redefined the cellular origins of periocular connective tissues interacting with the EOMs, which do not arise exclusively from neural crest mesenchyme as previously thought. Using 3D imaging approaches, we established an integrative blueprint for the EOM functional unit. By doing so, we identified a developmental time window in which individual EOMs emerge from a unique muscle anlage and establish insertions in the sclera, which sets these muscles apart from classical muscle-to-bone type of insertions. Further, we demonstrate that the eyeballs are a source of diffusible all-trans retinoic acid (ATRA) that allow their targeting by the EOMs in a temporal and dose-dependent manner. Using genetically modified mice and inhibitor treatments, we find that endogenous local variations in the concentration of retinoids contribute to the establishment of tendon condensations and attachment sites that precede the initiation of muscle patterning. Collectively, our results highlight how global and site-specific programs are deployed for the assembly of muscle functional units with precise definition of muscle shapes and topographical wiring of their tendon attachments.
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| 2. |
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| 3. |
- Vallecillo-Garcia, Pedro, et al.
(författare)
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A local subset of mesenchymal cells expressing the transcription factor Osr1 orchestrates lymph node initiation
- 2023
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Ingår i: Immunity. - : Cell Press. - 1074-7613 .- 1097-4180. ; 56:6, s. 1204-
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Tidskriftsartikel (refereegranskat)abstract
- During development, lymph node (LN) initiation is coordinated by lymphoid tissue organizer (LTo) cells that attract lymphoid tissue inducer (LTi) cells at strategic positions within the embryo. The identity and function of LTo cells during the initial attraction of LTi cells remain poorly understood. Using lineage tracing, we demon-strated that a subset of Osr1-expressing cells was mesenchymal LTo progenitors. By investigating the het-erogeneity of Osr1+ cells, we uncovered distinct mesenchymal LTo signatures at diverse anatomical loca-tions, identifying a common progenitor of mesenchymal LTos and LN-associated adipose tissue. Osr1 was essential for LN initiation, driving the commitment of mesenchymal LTo cells independent of neural ret-inoic acid, and for LN-associated lymphatic vasculature assembly. The combined action of chemokines CXCL13 and CCL21 was required for LN initiation. Our results redefine the role and identity of mesenchymal organizer cells and unify current views by proposing a model of cooperative cell function in LN initiation.
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