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Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs.

ABSTRACT: Dlx transcription factors are implicated in patterning the mammalian jaw, based on their nested expression patterns in the first branchial arch (primordium for jaw) and mutant phenotypes; inactivation of Dlx1 and Dlx2 (Dlx1/2-/-) causes defects in the upper jaw, whereas Dlx5/6(-/-) results in homeotic transformation of the lower jaw into upper jaw. Therefore, the 'Dlx codes' appear to regionalize the jaw primordium such that Dlx1/2 regulate upper jaw development, while Dlx5/6 confer the lower jaw fate. Towards identifying the genetic pathways downstream of Dlx5/6, we compared the gene expression profiles of the wild-type and Dlx5/6(-/-) mouse mandibular arch (prospective lower jaw). We identified 20 previously unrecognized Dlx5/6-downstream genes, of which 12 were downregulated and 8 upregulated in the mutant. We found a Dlx-regulated transcriptional enhancer in close proximity to Gbx2, one of the Dlx5/6-downstream genes, strongly suggesting that Gbx2 is a direct target of Dlx5/6. We also showed that Pou3f3 is normally expressed in the maxillary (prospective upper jaw) but not mandibular arch, is upregulated in the mandibular arch of Dlx5/6(-/-), and is essential for formation of some of the maxillary arch-derived skeleton. A comparative analysis of the morphological and molecular phenotypes of various Dlx single and double mutants revealed that Dlx1, 2, 5 and 6 act both partially redundantly and antagonistically to direct differential expression of downstream genes in each domain of the first branchial arch. We propose a new model for Dlx-mediated mammalian jaw patterning.

SUBMITTER: Jeong J

PROVIDER: S-EPMC4913551 | biostudies-other | 2008 Sep

REPOSITORIES: biostudies-other

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Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs.

Jeong Juhee J Li Xue X McEvilly Robert J RJ Rosenfeld Michael G MG Lufkin Thomas T Rubenstein John L R JL

Development (Cambridge, England) 20080901 17

Dlx transcription factors are implicated in patterning the mammalian jaw, based on their nested expression patterns in the first branchial arch (primordium for jaw) and mutant phenotypes; inactivation of Dlx1 and Dlx2 (Dlx1/2-/-) causes defects in the upper jaw, whereas Dlx5/6(-/-) results in homeotic transformation of the lower jaw into upper jaw. Therefore, the 'Dlx codes' appear to regionalize the jaw primordium such that Dlx1/2 regulate upper jaw development, while Dlx5/6 confer the lower ja ...[more]

PMID: 18697905

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Project description:IntroductionThe effects of manipulated dental occlusion on body posture has been investigated quite often and discussed controversially in the literature. Far less attention has been paid to the influence of dental occlusion position on human movement. If human movement was analysed, it was mostly while walking and not while running. This study was therefore designed to identify the effect of lower jaw positions on running behaviour according to different dental occlusion positions.MethodsTwenty healthy young recreational runners (mean age = 33.9±5.8 years) participated in this study. Kinematic data were collected using an eight-camera Vicon motion capture system (VICON Motion Systems, Oxford, UK). Subjects were consecutively prepared with four different dental occlusion conditions in random order and performed five running trials per test condition on a level walkway with their preferred running shoes. Vector based pattern recognition methods, in particular cluster analysis and support vector machines (SVM) were used for movement pattern identification.ResultsSubjects exhibited unique movement patterns leading to 18 clusters for the 20 subjects. No overall classification of the splint condition could be observed. Within individual subjects different running patterns could be identified for the four splint conditions. The splint conditions lead to a more symmetrical running pattern than the control condition.DiscussionThe influence of an occlusal splint on running pattern can be confirmed in this study. Wearing a splint increases the symmetry of the running pattern. A more symmetrical running pattern might help to reduce the risk of injuries or help in performance. The change of the movement pattern between the neutral condition and any of the three splint conditions was significant within subjects but not across subjects. Therefore the dental splint has a measureable influence on the running pattern of subjects, however subjects individuality has to be considered when choosing the optimal splint condition for a specific subject.

Project description:The evolution of the mammalian jaw during the transition from non-mammalian synapsids to crown mammals is a key event in vertebrate history and characterised by the gradual reduction of its individual bones into a single element and the concomitant transformation of the jaw joint and its incorporation into the middle ear complex. This osteological transformation is accompanied by a rearrangement and modification of the jaw adductor musculature, which is thought to have allowed the evolution of a more-efficient masticatory system in comparison to the plesiomorphic synapsid condition. While osteological characters relating to this transition are well documented in the fossil record, the exact arrangement and modifications of the individual adductor muscles during the cynodont-mammaliaform transition have been debated for nearly a century. We review the existing knowledge about the musculoskeletal evolution of the mammalian jaw adductor complex and evaluate previous hypotheses in the light of recently documented fossils that represent new specimens of existing species, which are of central importance to the mammalian origins debate. By employing computed tomography (CT) and digital reconstruction techniques to create three-dimensional models of the jaw adductor musculature in a number of representative non-mammalian cynodonts and mammaliaforms, we provide an updated perspective on mammalian jaw muscle evolution. As an emerging consensus, current evidence suggests that the mammal-like division of the jaw adductor musculature (into deep and superficial components of the m. masseter, the m. temporalis and the m. pterygoideus) was completed in Eucynodontia. The arrangement of the jaw adductor musculature in a mammalian fashion, with the m. pterygoideus group inserting on the dentary was completed in basal Mammaliaformes as suggested by the muscle reconstruction of Morganucodon oehleri. Consequently, transformation of the jaw adductor musculature from the ancestral ('reptilian') to the mammalian condition must have preceded the emergence of Mammalia and the full formation of the mammalian jaw joint. This suggests that the modification of the jaw adductor system played a pivotal role in the functional morphology and biomechanical stability of the jaw joint.

Project description:Distinct shaping of the upper versus lower facial skeleton is essential for function of the vertebrate jaw and middle ear, yet the cellular mechanisms by which this occurs have remained unclear. Here, we show that Endothelin1 (Edn1) signaling accelerates mesenchymal condensation and subsequent cartilage formation in the lower face through antagonism of Jagged-Notch signaling and Prrx1 transcription factors. A genomic analysis of facial skeletal precursors in mutants and overexpression embryos reveals that Jagged-Notch signaling represses genes that are strongly induced as pharyngeal arch neural crest-derived cells begin skeletal differentiation. In wild types, initial Jagged-Notch repression dorsally ensures that barx1+ condensations and cartilage differentiation occur first in ventral-intermediate zones of the pharyngeal arches. Reduced Jagged-Notch signaling results in an expansion of pre-cartilage condensations in the upper face, with loss of barx1 partially restoring dorsal cartilage shapes in jag1b mutants. Further, by studying new mutants for zebrafish prrx1a and prrx1b, we find that Prrx1 genes function in parallel to Jagged-Notch signaling to restrict the formation of dorsal barx1+ pre-cartilage condensations. Consistently, combined losses of jag1b and prrx1a/b robustly rescue ventral barx1+ condensations and lower facial cartilage development in edn1 mutants. Together, our work suggests that Edn1 works through parallel inhibition of Jagged-Notch and Prrx1 pathways to promote an earlier and more extensive establishment of cartilage condensations in the lower face. We performed RNAseq on FACS-sorted neural crest-derived pharyngeal arch cells (fli1a:GFP; sox10:DsRed double positive) from wild-type embryos at 3 different stages (20, 28, and 36 hours post fertilization) and embryos with altered levels of Edn1 and Notch signaling (edn1 mutants and hsp70I:Gal4; UAS:Edn1 transgenics; jag1b mutants, dibenzazepine-treated embryos, and hsp70I:Gal4; UAS:NICD transgenics. We also sequenced RNA from heat-shocked UAS:Edn1+ and hsp70I:Gal4+ transgenics and jag1b+/+ controls.

Dataset Information

Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs.

Publications

Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs.

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