Cranial neural crest cells (cNCCs) originate in the anterior neural tube and populate pharyngeal arches in which they contribute to formation of bone and cartilage. This cell population also provides molecular signals for the development of tissues of non-neural crest origin, such as the tongue muscles, teeth enamel or gland epithelium. Here we show that the transcription factor Meis2 is expressed in the oral region of the first pharyngeal arch (PA1) and later in the tongue primordium. Conditional inactivation of Meis2 in cNCCs resulted in loss of Sonic hedgehog signalling in the oropharyngeal epithelium and impaired patterning of PA1 along the lateral-medial and oral-aboral axis. Failure of molecular specification of PA1, illustrated by altered expression of Hand1/2, Dlx5, Barx1, Gsc and other markers, led to hypoplastic tongue and ectopic ossification of the mandible. Meis2-mutant mice thus display craniofacial defects that are reminiscent of several human syndromes and patients with mutations in the Meis2 gene.

• Klíčová slova
• Craniofacial, Meis, Pharyngeal arch, Sonic hedgehog (Shh) signalling,
• MeSH
• alely MeSH
• biologické markery MeSH
• crista neuralis cytologie   embryologie   MeSH
• delece genu MeSH
• fenotyp MeSH
• homeodoménové proteiny genetika   metabolismus   MeSH
• imunohistochemie MeSH
• kalcinóza genetika   metabolismus   MeSH
• mandibula embryologie   MeSH
• myši transgenní MeSH
• myši MeSH
• organogeneze genetika   MeSH
• proteiny hedgehog metabolismus   MeSH
• rozvržení tělního plánu * genetika   MeSH
• signální transdukce * MeSH
• zubní oblouk embryologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• homeodoménové proteiny MeSH
• Mrg1 protein, mouse MeSH Prohlížeč
• proteiny hedgehog MeSH

BACKGROUND: Comparative transcriptomics can answer many questions in developmental and evolutionary developmental biology. Most transcriptomic studies start by showing global patterns of variation in transcriptomes that differ between species or organs through developmental time. However, little is known about the kinds of expression differences that shape these patterns. RESULTS: We compared transcriptomes during the development of two morphologically distinct serial organs, the upper and lower first molars of the mouse. We found that these two types of teeth largely share the same gene expression dynamics but that three major transcriptomic signatures distinguish them, all of which are shaped by differences in the relative abundance of different cell types. First, lower/upper molar differences are maintained throughout morphogenesis and stem from differences in the relative abundance of mesenchyme and from constant differences in gene expression within tissues. Second, there are clear time-shift differences in the transcriptomes of the two molars related to cusp tissue abundance. Third, the transcriptomes differ most during early-mid crown morphogenesis, corresponding to exaggerated morphogenetic processes in the upper molar involving fewer mitotic cells but more migrating cells. From these findings, we formulate hypotheses about the mechanisms enabling the two molars to reach different phenotypes. We also successfully applied our approach to forelimb and hindlimb development. CONCLUSIONS: Gene expression in a complex tissue reflects not only transcriptional regulation but also abundance of different cell types. This knowledge provides valuable insights into the cellular processes underpinning differences in organ development. Our approach should be applicable to most comparative developmental contexts.

• Klíčová slova
• Comparative transcriptomics, Developmental biology, Heterochrony, Serial homology, Temporal dynamics of gene expression, Tooth, Transcriptomic signature,
• MeSH
• epitel embryologie   metabolismus   MeSH
• mezoderm embryologie   metabolismus   MeSH
• moláry embryologie   metabolismus   MeSH
• morfogeneze genetika   MeSH
• mozaicismus MeSH
• myši MeSH
• organogeneze genetika   MeSH
• signální transdukce MeSH
• transkriptom * MeSH
• vývojová biologie * metody   MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The fibroblast growth factors (FGFs) constitute one of the largest growth factor families, and several ligands and receptors in this family are known to play critical roles during tongue development. In order to provide a comprehensive foundation for research into the role of FGFs during the process of tongue formation, we measured the transcript levels by quantitative PCR and mapped the expression patterns by in situ hybridization of all 22 Fgfs during mouse tongue development between embryonic days (E) 11.5 and E14.5. During this period, Fgf5, Fgf6, Fgf7, Fgf9, Fgf10, Fgf13, Fgf15, Fgf16 and Fgf18 could all be detected with various intensities in the mesenchyme, whereas Fgf1 and Fgf2 were expressed in both the epithelium and the mesenchyme. Our results indicate that FGF signaling regulates tongue development at multiple stages.

• Klíčová slova
• Expression, FGF, Papilla, Tongue,
• MeSH
• embryo savčí metabolismus   MeSH
• embryonální vývoj genetika   MeSH
• epitel růst a vývoj   metabolismus   MeSH
• fibroblastové růstové faktory biosyntéza   genetika   MeSH
• hybridizace in situ MeSH
• jazyk růst a vývoj   metabolismus   MeSH
• mezoderm růst a vývoj   metabolismus   MeSH
• myši MeSH
• organogeneze genetika   MeSH
• signální transdukce MeSH
• vývojová regulace genové exprese genetika   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• fibroblastové růstové faktory MeSH