Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype
| Autor: | Ramada R. Khasawneh, Simon D. Bamforth, Helen M. Phillips, Timothy J. Mohun, Jürgen E. Schneider, Stéphane Zaffran, Heiko Peters, Ralf Kist, Rachel Queen, Rafiqul Hussain, Jonathan Coxhead |
|---|---|
| Přispěvatelé: | Newcastle University [Newcastle], Yarmouk University (YU), University of Leeds, The Francis Crick Institute [London], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Malbec, Odile |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Model organisms
Aortic arch Pathology medicine.medical_specialty QH301-705.5 [SDV]Life Sciences [q-bio] Cardiovascular development Pharyngeal endoderm Haploinsufficiency Biology Cardiovascular System Imaging 03 medical and health sciences Mice Neural crest 0302 clinical medicine medicine.artery medicine Animals Biology (General) 030304 developmental biology MSX1 Transcription Factor Mice Knockout 0303 health sciences Research Hyoid bone Embryogenesis Interrupted aortic arch medicine.disease Pax9 [SDV] Life Sciences [q-bio] stomatognathic diseases medicine.anatomical_structure Branchial Region Phenotype PAX9 Transcription Factor Neural crest cell migration 030217 neurology & neurosurgery Msx1 Developmental Biology Artery |
| Zdroj: | BMC Developmental Biology, Vol 21, Iss 1, Pp 1-20 (2021) BMC Developmental Biology BMC Developmental Biology, BioMed Central, 2021, 21 (1), pp.14. ⟨10.1186/s12861-021-00245-5⟩ BMC Developmental Biology, 2021, 21 (1), pp.14. ⟨10.1186/s12861-021-00245-5⟩ |
| ISSN: | 1471-213X |
| DOI: | 10.1186/s12861-021-00245-5⟩ |
| Popis: | Background Successful embryogenesis relies on the coordinated interaction between genes and tissues. The transcription factors Pax9 and Msx1 genetically interact during mouse craniofacial morphogenesis, and mice deficient for either gene display abnormal tooth and palate development. Pax9 is expressed specifically in the pharyngeal endoderm at mid-embryogenesis, and mice deficient for Pax9 on a C57Bl/6 genetic background also have cardiovascular defects affecting the outflow tract and aortic arch arteries giving double-outlet right ventricle, absent common carotid arteries and interruption of the aortic arch. Results In this study we have investigated both the effect of a different genetic background and Msx1 haploinsufficiency on the presentation of the Pax9-deficient cardiovascular phenotype. Compared to mice on a C57Bl/6 background, congenic CD1-Pax9–/– mice displayed a significantly reduced incidence of outflow tract defects but aortic arch defects were unchanged. Pax9–/– mice with Msx1 haploinsufficiency, however, have a reduced incidence of interrupted aortic arch, but more cases with cervical origins of the right subclavian artery and aortic arch, than seen in Pax9–/– mice. This alteration in arch artery defects was accompanied by a rescue in third pharyngeal arch neural crest cell migration and smooth muscle cell coverage of the third pharyngeal arch arteries. Although this change in phenotype could theoretically be compatible with post-natal survival, using tissue-specific inactivation of Pax9 to maintain correct palate development whilst inducing the cardiovascular defects was unable to prevent postnatal death in the mutant mice. Hyoid bone and thyroid cartilage formation were abnormal in Pax9–/– mice. Conclusions Msx1 haploinsufficiency mitigates the arch artery defects in Pax9–/– mice, potentially by maintaining the survival of the 3rd arch artery through unimpaired migration of neural crest cells to the third pharyngeal arches. With the neural crest cell derived hyoid bone and thyroid cartilage also being defective in Pax9–/– mice, we speculate that the pharyngeal endoderm is a key signalling centre that impacts on neural crest cell behaviour highlighting the ability of cells in different tissues to act synergistically or antagonistically during embryo development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|