1. Spatio-temporal dynamics of gene expression of the Edn1-Dlx5/6 pathway during development of the lower jaw
- Author
-
Hiroki Kurihara, Eglantine Heude, Giovanni Levi, Maxence Vieux-Rochas, Gérard Couly, Simonetta Astigiano, Ottavia Barbieri, Giorgio R. Merlo, Stefano Mantero, Evolution des régulations endocriniennes (ERE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Département Adaptations du vivant (AVIV), Muséum national d'Histoire naturelle (MNHN), Universita degli studi di Genova, Istituto di ricovero e cura a carattere scientifico Azienda Ospedaliera Universitaria 'San Martino' (IRCCS AOU San Martino), Laboratoire d'embryologie cellulaire et moléculaire (LECM), Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), School of Life Sciences [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), Department of Experimental Medicine, University of Genova, Istituto Nazionale per la Ricerca sul Cancro, Università degli studi di Genova = University of Genoa (UniGe), and Heude, Eglantine
- Subjects
[SDV.BA] Life Sciences [q-bio]/Animal biology ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Ectoderm ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Mandible ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,pharyngeal arches ,Mice ,0302 clinical medicine ,Endocrinology ,Basic Helix-Loop-Helix Transcription Factors ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,In Situ Hybridization ,ComputingMilieux_MISCELLANEOUS ,Genetics ,Mice, Knockout ,0303 health sciences ,Reverse Transcriptase Polymerase Chain Reaction ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,Neural crest ,Gene Expression Regulation, Developmental ,DLX6 ,DLX5 ,craniofacial development ,Phenotype ,medicine.anatomical_structure ,embryonic structures ,endothelin-1 ,cranial neural crest cells ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Endoderm ,HAND2 ,Signal Transduction ,Dlx ,Morphogenesis ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,[SDV.BDLR.RS]Life Sciences [q-bio]/Reproductive Biology/Sexual reproduction ,allelic dosage ,03 medical and health sciences ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,[SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,medicine ,Animals ,Humans ,RNA, Messenger ,first arch syndromes ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,030304 developmental biology ,Homeodomain Proteins ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology ,[SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Cell Biology ,Embryo, Mammalian ,[SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis ,Jaw ,biology.protein ,Neuroscience ,030217 neurology & neurosurgery - Abstract
International audience; The morphogenesis of the vertebrate skull results from highly dynamic integrated processes involving the exchange of signals between the ectoderm, the endoderm, and cephalic neural crest cells (CNCCs). Before migration CNCCs are not committed to form any specific skull element, molecular signals exchanged in restricted regions of tissue interaction are crucial in providing positional identity to the CNCCs mesenchyme and activate the specific morphogenetic process of different skeletal components of the head. In particular, the endothelin‐1 (Edn1)‐dependent activation of Dlx5 and Dlx6 in CNCCs that colonize the first pharyngeal arch (PA1) is necessary and sufficient to specify maxillo‐mandibular identity. Here, to better analyze the spatio‐temporal dynamics of this process, we associate quantitative gene expression analysis with detailed examination of skeletal phenotypes resulting from combined allelic reduction of Edn1, Dlx5, and Dlx6. We show that Edn1‐dependent and ‐independent regulatory pathways act at different developmental times in distinct regions of PA1. The Edn1→Dlx5/6→Hand2 pathway is already active at E9.5 during early stages of CNCCs colonization. At later stages (E10.5) the scenario is more complex: we propose a model in which PA1 is subdivided into four adjacent territories in which distinct regulations are taking place. This new developmental model may provide a conceptual framework to interpret the craniofacial malformations present in several mouse mutants and in human first arch syndromes. More in general, our findings emphasize the importance of quantitative gene expression in the fine control of morphogenetic events. genesis
- Published
- 2010