Bone marrow stromal cells (BMSCs) are versatile mesenchymal cell populations underpinning the major functions of skeleton, a majority which adjoin sinusoidal blood vessels and express C-X-C motif chemokine ligand 12 (CXCL12). However, how these activated during regeneration facilitate osteogenesis remains largely unknown. Cell-lineage analysis using Cxcl12-creER mice reveals that quiescent Cxcl12-creER+ perisinusoidal BMSCs differentiate into cortical bone osteoblasts solely regeneration. A...

Chondrocytes in the resting zone of postnatal growth plate are characterized by slow cell cycle progression, and encompass a population parathyroid hormone-related protein (PTHrP)-expressing skeletal stem cells that contribute to formation columnar chondrocytes. However, how these chondrocytes maintained remains undefined. We undertook genetic pulse-chase approach isolate cycling, label-retaining (LRCs) using chondrocyte-specific doxycycline-controllable Tet-Off system regulating expression...

Development of the craniofacial skeleton requires interactions between progenitor cells and collagen-rich extracellular matrix (ECM). The mediators these are not well-defined. Mutations in discoidin domain receptor 2 gene ( DDR2 ), which encodes a non-integrin collagen receptor, associated with human abnormalities, such as midface hypoplasia open fontanels. However, exact role this morphogenesis is known. As will be shown, Ddr2 -deficient mice exhibit defects bones including impaired...

Abstract Discoidin Domain Receptor 2 (DDR2) is a collagen-activated receptor kinase that, together with integrins, required for cells to respond the extracellular matrix. Ddr2 loss-of-function mutations in humans and mice cause severe defects skeletal growth development. However, cellular functions of bone are not understood. Expression lineage analysis showed selective expression at early stages formation resting zone proliferating chondrocytes periosteum. Consistent these findings, + could...

Craniofacial anomalies, especially midline facial defects, are among the most common birth defects in patients associated with increased mortality or require lifelong treatment. During mammalian embryogenesis, specific instructions arising at genetic, signaling, and metabolic levels important for stem cell behaviors fate determination, but how these functionally relevant mechanisms coordinated to regulate craniofacial morphogenesis remain unknown. Here, we report that BMP signaling cranial...

Large-scale sequencing efforts have captured a rapidly growing catalogue of genetic variations. However, the accurate establishment gene variant pathogenicity remains central challenge in translating personal genomics information to clinical decisions. Interferon Regulatory Factor 6 (IRF6) variants are significant contributors orofacial clefts. Although approximately three hundred IRF6 been documented, their effects on protein functions remain difficult interpret. Here, we demonstrate human...

Wnt signaling plays a critical role in craniofacial patterning, as well tooth and bone development. Rspo2 Rspo3 are key regulators of signaling. However, their coordinated function relative requirement development odontogensis poorly understood. We showed that zebrafish rspo2 rspo3 both expressed osteoprogenitors the embryonic skeleton. This is contrast to mouse development, where while expression not observed. In zebrafish, broadly pulp, odontoblasts epithelial crypts. developing molars...

Irf6 and Esrp1 are important for palate development across vertebrates. In zebrafish, we found that irf6 regulates the expression of esrp1. We detailed overlapping Esrp1/2 in mouse orofacial epithelium. esrp1/2 share periderm, frontonasal ectoderm, oral Genetic disruption zebrafish resulted cleft anterior neurocranium. The mutant also developed mouth opening. Lineage tracing cranial neural crest cells revealed not from migration defect, but impaired chondrogenesis. Analysis aberrant within...

Wnt signaling plays crucial roles in embryonic patterning including the regulation of convergent extension (CE) during gastrulation, establishment dorsal axis, and later, craniofacial morphogenesis. Further, is a regulator The adapter proteins Dact1 Dact2 modulate pathway through binding to Disheveled. However, distinct relative functions embryogenesis remain unclear. We found that dact1 dact2 genes have dynamic spatiotemporal expression domains are reciprocal one another suggesting...

The extracellular matrix (ECM) niche plays a critical role in determining cellular behavior during bone development including the differentiation and lineage allocation of skeletal progenitor cells to chondrocytes, osteoblasts, or marrow adipocytes. As major ECM component mineralized tissues, collagen has instructive as well structural roles is required for cell differentiation. Cells sense their environment using specific surface receptors. For many years, β1 integrins were considered main...

Wnt signaling plays a crucial role in the early embryonic patterning and development, to regulate convergent extension during gastrulation establishment of dorsal axis. Further, is regulator craniofacial morphogenesis. The adapter proteins Dact1 Dact2 modulate pathway through binding Disheveled. However, distinct relative functions embryogenesis remain unclear. We found that dact1 dact2 genes have dynamic spatiotemporal expression domains are reciprocal one another wnt11f2 , suggest...

The cranial base contains a special type of growth plate termed the synchondrosis, which functions as center skull. synchondrosis is composed bidirectional opposite-facing layers resting, proliferating, and hypertrophic chondrocytes, lacks secondary ossification center. In long bones, resting zone epiphyseal houses population parathyroid hormone-related protein (PTHrP)-expressing chondrocytes that contribute to formation columnar chondrocytes. Whether PTHrP+ in possess similar remains...

Summary BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1 ( ca‐Acvr1 ) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced tissue specific manner. However, L35 shows restricted expression pattern the transgene. Here, we another line, A11, using embryonic stem (ES) transgenesis. The A11 distinctive phenotypes from L35, along with very limited...

Wnt signaling plays a crucial role in the early embryonic patterning and development, to regulate convergent extension during gastrulation establishment of dorsal axis. Further, is regulator craniofacial morphogenesis. The adapter proteins Dact1 Dact2 modulate pathway through binding Disheveled, however, distinct relative functions embryogenesis remain unclear. We found that dact1 dact2 genes have dynamic spatiotemporal expression domains are reciprocal one another wnt11f2l , suggest...

Purpose: The intricate process of craniofacial development is orchestrated by the WNT signaling pathway, which directly impacts formation and anomalies orofacial structures. Within this adapter proteins DACT1 DACT2 emerge as pivotal players. Interestingly, gene variants have been implicated in congenital abnormalities observed kidney urinary tract (CAKUT) patients. A substantial 37% these CAKUT patients with alterations also present aberrations. Adding to complexity, certain clinical traits...

Wnt signaling plays crucial roles in embryonic patterning including the regulation of convergent extension during gastrulation, establishment dorsal axis, and later, craniofacial morphogenesis. Further, is a regulator The adapter proteins Dact1 Dact2 modulate pathway through binding to Disheveled. However, distinct relative functions embryogenesis remain unclear. We found that dact1 dact2 genes have dynamic spatiotemporal expression domains are reciprocal one another suggesting zebrafish...

Wnt signaling plays crucial roles in embryonic patterning including the regulation of convergent extension (CE) during gastrulation, establishment dorsal axis, and later, craniofacial morphogenesis. Further, is a regulator The adapter proteins Dact1 Dact2 modulate pathway through binding to Disheveled. However, distinct relative functions embryogenesis remain unclear. We found that dact1 dact2 genes have dynamic spatiotemporal expression domains are reciprocal one another suggesting...

Abstract Chondrocytes in the resting zone of postnatal growth plate are characterized by slow cell cycle progression, and encompass a population parathyroid hormone-related protein (PTHrP)-expressing skeletal stem cells that contribute to formation columnar chondrocytes. However, how these chondrocytes maintained remains undefined. We undertook genetic pulse-chase approach isolate cycling, label-retaining (LRCs) from using chondrocyte-specific doxycycline-controllable Tet-Off system...