Project description: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 single-cell RNA-seq analysis followed by in situ analysis of gene expression profiles, we show that Shh and Bmp4 signaling pathways are activated in a complementary pattern along the oral-aboral axis in mouse embryonic mandibular arch. Tissue-specific inactivation of hedgehog signaling in neural crest-derived mandibular mesenchyme led to expansion of BMP signaling activity to throughout the oral-aboral axis of the distal mandibular arch and subsequently duplication of dentary bone in the oral side of the mandible at the expense of tongue formation. Further studies indicate that hedgehog signaling acts through the Foxf1/2 transcription factors to specify the oral fate and pattern the oral-aboral axis of the mandibular mesenchyme.
Project description:The overall goal of this project is to investigate the role of TGF-beta signaling in tissue-tissue interactions between myogenic precursors of craniofacial muscles and cranial neural crest cells (CNCCs). Here, we conducted gene expression profiling of the mandibular arch from mice at embryonic day E11.5 with a CNCC-specific conditional inactivation of the TGF-beta receptor type 1 gene Alk5. These mice provide a model of microglossia as well as disrupted extraocular and masticatory muscle development, which are congenital birth defects commonly observed in several syndromic conditions. To investigate the adverse effects of dysfunctional TGF-beta signaling on tissue-tissue interactions between CNCCs and myogenic precursors of craniofacial muscles, we analyzed mandibular arch tissue of mice with a CNCC-specific conditional inactivation of Alk5 (Wnt1-Cre; Alk5 fl/fl). We performed microarray analyses of the mandibular arch of Alk5 fl/fl control mice and Wnt1-Cre; Alk5 fl/fl mutant mice, collected at embryonic day E11.5 (n=4 per group).
Project description:Fusion of branchial arch derivatives is an essential event in the development of craniofacial architecture. A unique feature of the mandibular arch development is medial/lateral compartmentalization for the molecular networks. Those networks give rise to multiple region-specific organs, namely teeth, a tongue, salivary glands, and the supporting matrices such as bones and cartilages. We aimed to investigate molecular networks that govern the fusion process during mouse mandibular development. To this end, cDNA microarray technology was employed for screening of spatio-temporal gene expression in developing mandibular arch from E9.7 through E14.5.
Project description:The overall goal of this project is to investigate the role of TGF-beta signaling in tissue-tissue interactions between myogenic precursors of craniofacial muscles and cranial neural crest cells (CNCCs). Here, we conducted gene expression profiling of the mandibular arch from mice at embryonic day E11.5 with a CNCC-specific conditional inactivation of the TGF-beta receptor type 1 gene Alk5. These mice provide a model of microglossia as well as disrupted extraocular and masticatory muscle development, which are congenital birth defects commonly observed in several syndromic conditions.
Project description:Fusion of branchial arch derivatives is an essential event in the development of craniofacial architecture. A unique feature of the mandibular arch development is medial/lateral compartmentalization for the molecular networks. Those networks give rise to multiple region-specific organs, namely teeth, a tongue, salivary glands, and the supporting matrices such as bones and cartilages. We aimed to investigate molecular networks that govern the fusion process during mouse mandibular development. To this end, cDNA microarray technology was employed for screening of spatio-temporal gene expression in developing mandibular arch from E9.7 through E11.5. We conducted to divide a mandibular arch medially and laterally to compare both gene expression. From an embryo at E10.5, a medial (M) sample of the mandibular arch was dissected out -at just the distal end of opposed lateral lingual swellings-, and the bulk of remnant lateral region was collected as (L) sample under a stereomicroscope. Forty embryos for each time-point were used to obtain a pool of total RNA.
Project description:How the dorsal-ventral axis of the vertebrate jaw, particularly the position of tooth initiation site, is established remains a critical and unresolved question. Tooth development starts with the formation of the dental lamina, a localized thickened strip within the maxillary and mandibular epithelium. To identify transcriptional regulatory networks (TRN) controlling the specification of dental lamina from the naïve mandibular epithelium, we utilized Laser Microdissection coupled low-input RNA-seq (LMD-RNA-seq) to profile gene expression of different domains of the mandibular epithelium along the dorsal-ventral axis in wild type mouse and two loss-of-function mouse models of domain specific transcription factors.