Biology subjects

Ho, T.-V.

Publications and source records attributed to Ho, T.-V..

3 recordsLinked to original sources

bioRxiv2022

Canonical Wnt signaling regulates soft palate development through mediating ciliary homeostasis

Craniofacial morphogenesis requires complex interactions among tissues, signaling pathways, secreted factors, and organelles. The details of these interactions remain elusive. In this study, we analyzed the molecular mechanisms and homeostatic cellular activities governing soft palate development to improve regenerative strategies for cleft palate patients. We have identified canonical Wnt signaling as a key signaling pathway primarily active in cranial neural crest (CNC)-derived mesenchymal cells surrounding soft palatal myogenic cells. Using Osr2-Cre;{beta}-cateninfl/fl mice, we further discovered that Wnt signaling is indispensable for mesenchymal cell proliferation and subsequently myogenesis through mediating ciliogenesis. Specifically, we identified that Wnt signaling directly regulates expression of the ciliary gene Ttll3 through {beta}-catenin/Tcf7l2 complex. Impaired ciliary disassembly leads to differentiation defects of mesenchymal cells and indirectly disrupts myogenesis through decreased expression of Dlk1, a mesenchymal cell-derived pro-myogenesis factor. Moreover, we found that restoring ciliary homeostasis rescues mesenchymal cell proliferation in Osr2-Cre;{beta}-cateninfl/fl samples. This study highlights the role of Wnt signaling in palatogenesis through controlling ciliary homeostasis, which establishes a new mechanism for Wnt-regulated craniofacial morphogenesis.

developmental biology↗

bioRxiv2022

TGF-β signaling and Creb5 cooperatively regulate Fgf18 to control pharyngeal muscle development

The communication between myogenic cells and their surrounding connective tissues is indispensable for muscle morphogenesis. During late embryonic development in mice, myogenic progenitors migrate to discrete sites to form individual muscles. The detailed mechanism of this process remains unclear. Using levator veli palatini (LVP) development as a model, we systematically investigated how a distinct connective tissue subpopulation, perimysial fibroblasts, communcates with myogenic cells to regulate mouse pharyngeal myogenesis. Using single-cell RNAseq data analysis, we identified that TGF-{beta} signaling is a key regulator for the perimysial fibroblasts. Loss of TGF-{beta} signaling led to defects in perimysial fibroblasts and subsequently muscle formation in Osr2-Cre;Alk5fl/fl mice. In particular, a perimysial fibroblast-specific regulator, Creb5, interacts with TGF-{beta} signaling to enable specific activation of perimysial fibroblast-derived signals such as Fgf18. Moreover, Fgf18 supports pharyngeal muscle development in vivo and its exogenous expression can partially rescue myogenic cell numbers in Osr2-Cre;Alk5fl/fl samples, illustrating that TGF-{beta}-regulated Fgf18 signaling is required for LVP development. Collectively, our findings revealed the mechanism by which TGF-{beta} signaling achieves its specificity in defining the perimysial-to-myogenic signals for pharyngeal myogenesis.

developmental biology↗

bioRxiv2021

Kdm6b confers Tfdp1 with the competence to activate p53 signalling in regulating palatogenesis

Epigenetic regulation plays extensive roles in diseases and development. Disruption of epigenetic regulation not only increases the risk of cancer, but can also cause various developmental defects. However, it is still unclear how epigenetic regulators coordinate with tissue-specific regulatory factors during morphogenesis of specific organs. Using palatogenesis as a model, we reveal the functional significance of Kdm6b, a H3K27me3 demethylase, in regulating embryonic development. Our study shows that Kdm6b plays an essential role in neural crest development, and loss of Kdm6b disturbs p53 pathway-mediated activity, leading to complete cleft palate along with cell proliferation and differentiation defects. Furthermore, activity of H3K27me3 on the promoter of p53 is precisely controlled by Kdm6b, and Ezh2 in regulating p53 expression in cranial neural crest cells. More importantly, Kdm6b renders chromatin accessible to the transcription factor Tfdp1, which binds to the promoter of p53 along with Kdm6b to specifically activate p53 expression during palatogenesis. Collectively our results highlight the important role of the epigenetic regulator Kdm6b and how it cooperates with Tfdp1 to achieve its functional specificity in regulating p53 expression, and further provide mechanistic insights into the epigenetic regulatory network during organogenesis.

developmental biology↗