Cardiopharyngeal mesoderm origins of musculoskeletal and connective tissues in the mammalian pharynx

Adachi, Noritaka; Bilio, Marchesa; Baldini, Antonio; Kelly, Robert G.

doi:10.1242/dev.185256

Cited by 32 publications

(33 citation statements)

References 81 publications

(144 reference statements)

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“…At E13.5, the Foxg1Cre and Dermo1Creexpressing splanchnic mesoderm lineage traced Sox9+ tracheal chondrocytes, as well as the Foxf1+ mesenchyme and smooth muscle of the esophagus and dorsal trachea (Supplemental Figure 1A-C). In contrast, the Wnt1+ cells did not trace the tracheal chondrocytes or Foxf1+ smooth muscle (Supplemental Figure 1D), but, as previously reported, Wnt1-traced cells were only detected in laryngeal cartilage and neurons innervating the esophagus (data not shown) (Adachi et al, 2020;Tabler et al, 2017).…”

Section: Tracheal Chondrocytes Arise From the Splanchnic Foregut Mesosupporting

confidence: 82%

Disruption of a Hedgehog-Foxf1-Rspo2 Signaling Axis Leads to Tracheomalacia and a Loss of Sox9+ Tracheal Chondrocytes

Nasr

Chaturvedi

Agarwal

et al. 2020

Preprint

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Congenital tracheomalacia, resulting from incomplete tracheal cartilage development, is a relatively common birth defect that severely impairs breathing in neonates. Mutations in the Hedgehog (HH) pathway and downstream Gli transcription factors are associated with tracheomalacia in patients and mouse models; however, the underlying molecular mechanisms are unclear. Using multiple HH/Gli mouse mutants including one that mimics Pallister-Hall Syndrome, we show that excessive Gli repressor activity prevents specification of tracheal chondrocytes. Lineage tracing experiments show that Sox9+ chondrocytes arise from HH-responsive splanchnic mesoderm in the fetal foregut that expresses the transcription factor Foxf1. Disrupted HH/Gli signaling results in 1) loss of Foxf1 which in turn is required to support Sox9+ chondrocyte progenitors and 2) a dramatic reduction in Rspo2, a secreted ligand that potentiates Wnt signaling known to be required for chondrogenesis. These results reveal a HH-Foxf1-Rspo2 signaling axis that governs tracheal cartilage development and informs the etiology of tracheomalacia.SUMMARY STATEMENTThis work provides a mechanistic basis for tracheomalacia in patients with Hedgehog pathway mutations.

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Section: Tracheal Chondrocytes Arise From the Splanchnic Foregut Mesosupporting

confidence: 82%

Disruption of a Hedgehog-Foxf1-Rspo2 Signaling Axis Leads to Tracheomalacia and a Loss of Sox9+ Tracheal Chondrocytes

Nasr

Chaturvedi

Agarwal

et al. 2020

Preprint

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“…2). In some cases, separate condensations from these embryonic lineages integrate seamlessly to form the functional bone, such as in the temporal bone, the cranial base, the scapula, stapes, clavicle and thyroid cartilage [57][58][59][60][61][62] (also see review for scapula and pelvis 63 ) (Fig. 2).…”

Section: Different Embryonic Origins Of Bones: Does It Matter?mentioning

confidence: 99%

Making and shaping endochondral and intramembranous bones

Galea

Zein

Allen

et al. 2020

Developmental Dynamics

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Skeletal elements have a diverse range of shapes and sizes specialized to their various roles including protecting internal organs, locomotion, feeding, hearing, and vocalization. The precise positioning, size, and shape of skeletal elements is therefore critical for their function. During embryonic development, bone forms by endochondral or intramembranous ossification and can arise from the paraxial and lateral plate mesoderm or neural crest. This review describes inductive mechanisms to position and pattern bones within the developing embryo, compares and contrasts the intrinsic vs extrinsic mechanisms of endochondral and intramembranous skeletal development, and details known cellular processes that precisely determine skeletal shape and size. Key cellular mechanisms are employed at distinct stages of ossification, many of which occur in response to mechanical cues (eg, joint formation) or preempting future load‐bearing requirements. Rapid shape changes occur during cellular condensation and template establishment. Specialized cellular behaviors, such as chondrocyte hypertrophy in endochondral bone and secondary cartilage on intramembranous bones, also dramatically change template shape. Once ossification is complete, bone shape undergoes functional adaptation through (re)modeling. We also highlight how alterations in these cellular processes contribute to evolutionary change and how differences in the embryonic origin of bones can influence postnatal bone repair.

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“…The mesenchymal nature of the PDGFRA+; KDR− cell population is also consistent with high expression of genes encoding collagens and vimentin. Tbx1-expressing mesenchymal cells contribute to various tissues of the neck and face, including some muscle, bones, and connective tissue (Adachi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Chromatin and Transcriptional Response to Loss of TBX1 in Early Differentiation of Mouse Cells

Cirino

Aurigemma

Franzese

et al. 2020

Front. Cell Dev. Biol.

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The T-box transcription factor TBX1 has critical roles in the cardiopharyngeal lineage and the gene is haploinsufficient in DiGeorge syndrome, a typical developmental anomaly of the pharyngeal apparatus. Despite almost two decades of research, if and how TBX1 function triggers chromatin remodeling is not known. Here, we explored genome-wide gene expression and chromatin remodeling in two independent cellular models of Tbx1 loss of function, mouse embryonic carcinoma cells P19Cl6, and mouse embryonic stem cells (mESCs). The results of our study revealed that the loss or knockdown of TBX1 caused extensive transcriptional changes, some of which were cell type-specific, some were in common between the two models. However, unexpectedly we observed only limited chromatin changes in both systems. In P19Cl6 cells, differentially accessible regions (DARs) were not enriched in T-BOX binding motifs; in contrast, in mESCs, 34% (n = 47) of all DARs included a T-BOX binding motif and almost all of them gained accessibility in Tbx1 −/− cells. In conclusion, despite a clear transcriptional response of our cell models to loss of TBX1 in early cell differentiation, chromatin changes were relatively modest.

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Cardiopharyngeal mesoderm origins of musculoskeletal and connective tissues in the mammalian pharynx

Cited by 32 publications

References 81 publications

Disruption of a Hedgehog-Foxf1-Rspo2 Signaling Axis Leads to Tracheomalacia and a Loss of Sox9+ Tracheal Chondrocytes

Disruption of a Hedgehog-Foxf1-Rspo2 Signaling Axis Leads to Tracheomalacia and a Loss of Sox9+ Tracheal Chondrocytes

Making and shaping endochondral and intramembranous bones

Chromatin and Transcriptional Response to Loss of TBX1 in Early Differentiation of Mouse Cells

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