FGF signaling patterns cell fate at the interface between tendon and bone

Roberts, Ryan R.; Bobzin, Lauren; Teng, Camilla S; Pal, Deepanwita; Tuzon, Creighton T.; Schweitzer, Ronen; Merrill, Amy E.

doi:10.1242/dev.170241

Cited by 32 publications

(42 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SOX9 expression overlapped with that of PITX2 ( Fig 3D, 3H, S3E' and S3F' Fig) but became more restricted to the insertion site by E13.5 and with a pattern complementary to Scx-GFP+ ( Fig 3G and S3F Fig). Notably, Scx-GFP+ SOX9+ cells could be detected between E11.5 and E13.5 at the interface between mutually exclusive Scx-GFP+ and SOX9+ cells (S3A-S3C" Fig), resembling what was observed during tendon-to-bone attachment formation in other regions in the embryo [53][54][55][56].…”

Section: Plos Biologysupporting

confidence: 54%

“…superstructures or ridges, generated by a unique set of progenitors that co-express Scx and SRY-box containing gene 9 (SOX9), provide a stable anchoring point for muscles via tendons [53][54][55][56]. Although EOMs insert into a non-bone NCC-derived structure, early markers of precommitted cartilage, such as SOX9, are expressed in the POM [57].…”

Section: Plos Biologymentioning

confidence: 99%

“…As mammals do not develop a cartilage layer within the sclera [57,101], transient expression of SOX9 in the POM-ring of mouse embryos at the time of EOM patterning is intriguing. In the developing limb and jaw, tendon and bone are attached by a transitional connective tissue that develops from bipotent progenitors that co-express Scx and SOX9 [53][54][55][56], before progenitors are allocated to either cartilage or tendon lineages. Similarly, we observed a transient population of Scx-GFP/SOX9 double-positive cells at the insertion sites in the POM.…”

Section: Role Of Ra In the Integration Of Eom Patterning And Insertiomentioning

confidence: 99%

See 2 more Smart Citations

Local retinoic acid signaling directs emergence of the extraocular muscle functional unit

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Plos Biologysupporting

confidence: 54%

Section: Plos Biologymentioning

confidence: 99%

Section: Role Of Ra In the Integration Of Eom Patterning And Insertiomentioning

confidence: 99%

See 1 more Smart Citation

Local retinoic acid signaling directs emergence of the extraocular muscle functional unit

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Interactions between the mesoderm and neural crest co-ordinate the muscular skeletal development of the head [49]. A striking piece of evidence for the tendon origin of the disc is the expression in the developing articular disc of Scleraxis [13,50], a specific regulator of tendon and ligament development [51,52]. If the disc is derived from a tendon, then it may be thought of as a fibrocartilage sesamoid.…”

Section: Discussionmentioning

confidence: 99%

The TMJ disc is a common ancestral feature in all mammals, as evidenced by the presence of a rudimentary disc during monotreme development

Anthwal

Tucker

2020

Preprint

View full text Add to dashboard Cite

The novel mammalian jaw joint, known in humans as the temporomandibular joint or TMJ, is cushioned by a fibrocartilage disc. This disc is secondarily absent in therian mammals that have lost their dentition, such as giant anteaters and some baleen whales. The disc is also absent in all monotremes. However, it is not known if the absence in monotremes is secondary to the loss of dentition, or if it is an ancestral absence. We use museum held platypus and echidna histological sections to demonstrate that the developing monotreme jaw joint forms a disc primordium that fails to mature and become separated from the mandibular condyle. We then show that monotreme developmental anatomy is similar to that observed in transgenic mouse mutants with reduced musculature. We therefore suggest that the absence of the disc on monotremes is a consequence of the changes in jaw musculature associated with the loss of adult teeth. Taken together, these data indicate that the ancestors of extant monotremes likely had a jaw joint disc, and that the disc evolved in the last common ancestor or all mammals.

show abstract

“…Furthermore, both molecular and mechanical signals regulate the AU. TGFβ signaling regulates the specification of AU progenitors, whereas BMP and FGF signaling as well as mechanical signals determine their fate and differentiation [7,12,13]. Postnatal enthesis cells have been termed fibrocartilage cells based on their histological appearance, since they display morphological features that are shared with tenocytes and chondrocytes [14].…”

Section: Introductionmentioning

confidence: 99%

Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors

Kult

Zelzer

Olender

et al. 2020

Preprint

View full text Add to dashboard Cite

The connection between different tissues is vital for the development and function of any organs and systems. In the musculoskeletal system, the attachment of elastic tendons to stiff bones poses a mechanical challenge that is solved by the formation of a transitional tissue, which allows the transfer of muscle forces to the skeleton without tearing. Here, we show that tendon-to-bone attachment cells are bi-fated, activating a mixture of chondrocyte and tenocyte transcriptomes, which is regulated by sharing regulatory elements with these cells and by Krüppel-like factors transcription factors (KLF).To uncover the molecular identity of attachment cells, we first applied high-throughput RNA sequencing to murine humeral attachment cells. The results, which were validated by in situ hybridization and single-molecule in situ hybridization, reveal that attachment cells express hundreds of chondrogenic and tenogenic genes. In search for the underlying mechanism allowing these cells to express these genes, we performed ATAC sequencing and found that attachment cells share a significant fraction of accessible intergenic chromatin areas with either tenocytes or chondrocytes. Epigenomic analysis further revealed transcriptional enhancer signatures for the majority of these regions. We then examined a subset of these regions using transgenic mouse enhancer reporter. Results verified the shared activity of some of these enhancers, supporting the possibility that the transcriptome of attachment cells is regulated by enhancers with shared activities in tenocytes or chondrocytes. Finally, integrative chromatin and motif analyses, as well as the transcriptome data, indicated that KLFs are regulators of attachment cells. Indeed, blocking the expression of Klf2 and Klf4 in the developing limb mesenchyme led to abnormal differentiation of attachment cells, establishing these factors as key regulators of the fate of these cells.In summary, our findings show how the molecular identity of bi-fated attachment cells enables the formation of the unique transitional tissue that connect tendon to bone. More broadly, we show how mixing the transcriptomes of two cell types through shared enhancers and a dedicated set of transcription factors can lead to the formation of a new cell fate that connects them.

show abstract

FGF signaling patterns cell fate at the interface between tendon and bone

Cited by 32 publications

References 55 publications

Local retinoic acid signaling directs emergence of the extraocular muscle functional unit

Local retinoic acid signaling directs emergence of the extraocular muscle functional unit

The TMJ disc is a common ancestral feature in all mammals, as evidenced by the presence of a rudimentary disc during monotreme development

Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors

Contact Info

Product

Resources

About