Jingyue Xu

Cincinnati Children's Hospital Medical Center | CCHMC · Division of Developmental Biology

Mutations in SHH and several other genes encoding components of the Hedgehog signaling pathway have been associated with holoprosencephaly syndromes, with craniofacial anomalies ranging in severity from cyclopia to facial cleft to midfacial and mandibular hypoplasia. Studies in animal models have revealed that SHH signaling plays crucial roles at m...

The tongue is a highly specialized muscular organ with diverse cellular origins, which provides an excellent model for understanding mechanisms controlling tissue-tissue interactions during organogenesis. Previous studies showed that SHH signaling is required for tongue morphogenesis and tongue muscle organization, but little is known about the und...

Proper development of tendons is crucial for the integration and function of the musculoskeletal system. Currently little is known about the molecular mechanisms controlling tendon development and tendon cell differentiation. The transcription factor Scleraxis (Scx) is expressed throughout tendon development and plays essential roles in both embryo...

Disruption of FOXF2, encoding a member of the Forkhead family transcription factors, has been associated with cleft palate in humans and mice. FOXF2 is located in a conserved gene cluster containing FOXQ1, FOXF2, and FOXC1. We found that expression of Foxq1 is dramatically upregulated in the embryonic palatal mesenchyme in Foxf2–/– mouse embryos. W...

Cleft palate is among the most common structural birth defects in humans. Previous studies have shown that mutations in FOXF2 are associated with cleft palate in humans and mice and that Foxf2 acts in a Shh-Foxf-Fgf18-Shh molecular network controlling palatal shelf growth. In this study, we combined RNA-seq and ChIP-seq approaches to identify direc...

SIX1 and SIX2 encode closely related transcription factors of which disruptions have been associated with distinct craniofacial syndromes, with mutations in SIX1 associated with branchiootic syndrome 3 (BOS3) and heterozygous deletions of SIX2 associated with frontonasal dysplasia defects. Whereas mice deficient in Six1 recapitulated most of the de...

Development of vertebrate jaws involves patterning neural crest-derived mesenchyme cells into distinct subpopulations along the proximal-distal and oral-aboral axes. Although the molecular mechanisms patterning the proximal-distal axis have been well studied, little is known regarding the mechanisms patterning the oral-aboral axis. Using unbiased s...

Heterotopic ossification is the abnormal formation of mineralized bone in skin, muscle, tendon, or other soft tissues. Tendon ossification often occurs from acute tendon injury or chronic tendon degeneration, of which current treatment relies heavily on surgical removal of the ectopic bony tissues. Unfortunately, surgery creates additional trauma,...

Previous studies have identified the odd-skipped related 2 (Osr2) transcription factor as a key intrinsic regulator of palatal shelf growth and morphogenesis. However, little is known about the molecular program acting downstream of Osr2 in the regulation of palatogenesis. In this study, we isolated palatal mesenchyme cells from embryonic day 12.5...

During early fetal development, paracrine Hedgehog (HH) ligands secreted from the foregut epithelium activate Gli transcription factors in the surrounding mesenchyme to coordinate formation of the respiratory system, digestive track and the cardiovascular network. Although disruptions to this process can lead to devastating congenital defects, the...

Renal hypoplasia is a common cause of pediatric renal failure and several adult-onset diseases. Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality with kidney defects in homozygotes. How OSR1 regulates kidney development and nephron endowment is not we...

Osr1+/-Wt1+/- embryos exhibit defects in Six2-positive metanephric mesenchyme. (A-C) Whole mount immunofluorescent staining for Six2 protein (red) in E10.5 Osr1+/- (A), Wt+/- (B), and Osr1+/-Wt1+/- (C) embryos. The embryos were counterstained with DAPI (Blue). The white dotted line outlines the metanephric mesenchyme. Scale bar, 100 μm. (TIF)

Cleft palate is a common major birth defect for which currently known causes account for less than 30% of pathology in humans. In this study, we carried out mutagenesis screening in mice to identify new regulators of palatogenesis. Through genetic linkage mapping and whole exome sequencing, we identified a loss-of-function mutation in the Golgb1 ge...

Cleft palate is among the most common birth defects in humans. Previous studies have shown that Shh signaling plays critical roles in palate development and regulates expression of several members of the forkhead-box (Fox) family transcription factors, including Foxf1 and Foxf2, in the facial primordia. Although cleft palate has been reported in mi...

Differential expression analysis of the RNA-seq data in the Foxf2-/-Osr2RFP/+ palatal mesenchyme in comparison with the control palatal mesenchyme. (XLSX)

Primers used in real-time RT-PCR assay. (DOCX)

Comparison of Msx1, Bmp4, and Fgf10 mRNA expression patterns in wildtype and Foxf2-/- mutant embryos. (A-F) Whole-mount in situ hybridization detection of Msx1 (A, B), Bmp4 (C, D), and Fgf10 (E, F) mRNAs in the developing palatal shelves in wildtype (A, C, E) and Foxf2-/- mutant (B, D, F) embryos at E13.5. White dash lines indicate the palate regio...

Analysis of palate development defects in Foxf1c/cWnt1-Cre mutant mouse embryos. (A, B) Ventral view of stained skeletal preparations of Foxf1c/+Wnt1-Cre (A) and Foxf1c/cWnt1-Cre (B) neonatal skulls. Arrowheads indicate palatal processes of the palatine bones that have fused to each other in the Foxf1c/+Wnt1-Cre mice (A) but are absent in the Foxf1...

Comparison of expression of Fgf18 mRNAs in Foxf1c/cFoxf2c/c and Foxf1c/cFoxf2c/cWnt1-Cre mutant embryos. Frontal sections showing expression of Fgf18 mRNA in the anterior (A, B), middle (C, D) and posterior (E, F) regions of the developing palate in Foxf1c/cFoxf2c/c (A, C, E) and Foxf1c/cFoxf2c/cWnt1-Cre mutant (B, D, F) embryos at E12.5. p, palata...

Comparison of Shox2 and Barx1 mRNA expression patterns in Foxf1c/cFoxf2c/c and Foxf1c/cFoxf2c/cWnt1-Cre mutant embryos. (A-D) Whole-mount in situ hybridization detection of Shox2 mRNAs in the developing palatal shelves in Foxf1c/cFoxf2c/c (A, C) and Foxf1c/cFoxf2c/cWnt1-Cre mutant (B, D) embryos at E12.5 (A, B) and E13.5 (C, D). (E-H) Whole-mount i...

Comparison of expression of Fgf18 and Shh mRNAs in the palatal shelves in Foxf1c/+Wnt1-Cre and Foxf1c/cWnt1-Cre mutant embryos. (A, B) Whole-mount in situ hybridization detection of Fgf18 mRNAs in the developing palatal shelves in Foxf1c/c (A) and Foxf1c/cWnt1-Cre mutant (B) embryos at E13.5. (C, D) Whole-mount in situ hybridization detection of Sh...

Palatogenesis involves the initiation, growth, morphogenesis, and fusion of the primary and secondary palatal shelves from initially separate facial prominences during embryogenesis to form the intact palate separating the oral cavity from the nostrils. The palatal shelves consist mainly of cranial neural crest-derived mesenchymal cells covered by...

Tendons are fibrous connective tissues that transmit force between muscle and bone. Whereas the molecular and cellular mechanisms of bone and muscle development have been well studied, that of tendon development is poorly understood. Using the Scx-GFP transgenic mice, we isolated GFP(+) cells from the developing mouse limbs at E11.5, E13.5, and E15...

Colonic immune homeostasis is essential for normal gastrointestinal tract functioning. In this study, we report that specific gene targeting of phosphatase and tensin homolog (PTEN) in smooth muscle cells caused age-related colonic lymphoid hyperplasia followed by global immune activation in mice. Beginning at 5 weeks of age, these mutant mice disp...

Mammalian kidney organogenesis involves reciprocal epithelial-mesenchymal interactions that drive iterative cycles of nephron formation. Recent studies have demonstrated that the Six2 transcription factor acts cell autonomously to maintain nephron progenitor cells, whereas canonical Wnt signaling induces nephron differentiation. How Six2 maintains...

Significance Development of the tongue is a major vertebrate adaptation to terrestrial life. Interestingly, although the tongues of birds and mammals initially develop similarly, the bird tongue is underpinned by an extensive internal skeleton, whereas the oral part of the mammalian tongue is boneless, which is critical not only for feeding but als...

Bone morphogenetic protein (BMP) signaling pathway plays important roles in urinary tract development although the detailed regulation of its activity in this process remains unclear. Here we report that follistatin-like 1 (Fstl1), encoding a secreted extracellular glycoprotein, is expressed in developing ureter and antagonizes BMP signaling activi...

Induced pluripotent stem cells (iPSCs) can be reprogrammed from adult somatic cells by transduction with Oct4, Sox2, Klf4, and c-Myc, but the molecular cascades initiated by these factors remain poorly understood. Impeding their elucidation is the stochastic nature of the iPS induction process, which results in heterogeneous cell populations. Here...

Mammalian RNA editing catalyzed by adenosine deaminases acting on RNA (ADARs) ADAR1 and ADAR2 plays pivotal roles in the brain through functional modifications of neurotransmitter receptors and ion channels. We have demonstrated previously that RNA editing by ADAR2 is regulated metabolically in pancreatic β cells. To investigate the cellular functi...

Accumulating evidence suggests a role for Toll-like receptor (TLR) signaling at the intestinal epithelial cells (IECs) level for intestinal protection against exogenous injury or pathogenic infection. We hypothesized that MyD88 dependent TLR signaling at intestinal epithelium is critical for mucosal immune homeostasis. In the current study, a trans...

Wnt signaling plays a key role in embryogenesis and cancer development. Dvl (Dishevelled) is a central mediator for both the canonical and noncanonical Wnt pathways. Dact1 (Dapper1, Dpr1), a Dvl interactor, has been shown to negatively modulate Wnt signaling by promoting lysosomal degradation of Dvl. Here we report that Dact1-deficient mice have mu...

Mutants of brain-derived neurotrophic factor (BDNF) are associated with obesity. However, the regulatory mechanism of BDNF expression is still unclear. We developed a novel mutant mouse line, transgenic insertional mutants with obesity, named Timo, in which a potential regulatory locus of Bdnf was disrupted by transgene insertion. The insertion sit...