Journal article
MEMO1 drives cranial endochondral ossification and palatogenesis
Developmental biology, Vol.415(2), pp.278-295
07/15/2016
DOI: 10.1016/j.ydbio.2015.12.024
PMCID: PMC4914435
PMID: 26746790
Abstract
The cranial base is a component of the neurocranium and has a central role in the structural integration of the face, brain and vertebral column. Consequently, alteration in the shape of the human cranial base has been intimately linked with primate evolution and defective development is associated with numerous human facial abnormalities. Here we describe a novel recessive mutant mouse strain that presented with a domed head and fully penetrant cleft secondary palate coupled with defects in the formation of the underlying cranial base. Mapping and non-complementation studies revealed a specific mutation in Memo1 a gene originally associated with cell migration. Expression analysis of Memol identified robust expression in the perichondrium and periosteum of the developing cranial base, but only modest expression in the palatal shelves. Fittingly, although the palatal shelves failed to elevate in Memol mutants, expression changes were modest within the shelves themselves. In contrast, the cranial base, which forms via endochondral ossification had major reductions in the expression of genes responsible for bone formation, notably matrix metalloproteinases and markers of the osteoblast lineage, mirrored by an increase in markers of cartilage and extracellular matrix development. Concomitant with these changes, mutant cranial bases showed an increased zone of hypertrophic chondrocytes accompanied by a reduction in both vascular invasion and mineralization. Finally, neural crest cell-specific deletion of Memol caused a failure of anterior cranial base ossification indicating a cell autonomous role for MEMO1 in the development of these neural crest cell derived structures. However, palate formation was largely normal in these conditional mutants, suggesting a non-autonomous role for MEMO1 in palatal closure. Overall, these findings assign a new function to MEMO1 in driving endochondral ossification in the cranium, and also link abnormal development of the cranial base with more widespread effects on craniofacial shape relevant to human craniofacial dysmorphology. (C) 2015 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- MEMO1 drives cranial endochondral ossification and palatogenesis
- Creators
- Eric Van Otterloo - University of Colorado Anschutz Medical CampusWeiguo Feng - University of Colorado Anschutz Medical CampusKenneth L. Jones - University of Colorado DenverNancy E. Hynes - University of BaselDavid E. Clouthier - University of Colorado Anschutz Medical CampusLee Niswander - Children's Hospital ColoradoTrevor Williams - Children's Hospital Colorado
- Resource Type
- Journal article
- Publication Details
- Developmental biology, Vol.415(2), pp.278-295
- DOI
- 10.1016/j.ydbio.2015.12.024
- PMID
- 26746790
- PMCID
- PMC4914435
- NLM abbreviation
- Dev Biol
- ISSN
- 0012-1606
- eISSN
- 1095-564X
- Publisher
- Elsevier
- Number of pages
- 18
- Grant note
- F32DE02370; R01 DE019843 / National Institute of Dental and Craniofacial Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) Cleft Palate Foundation Research Support Grant R01HD081562 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) American Association of Anatomists Postdoctoral Fellowship P30CA046934 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA046934 / Biostatistics/Bioinformatics Shared Resources of Colorado's NIH/NCI Cancer Center F32DE023709 / NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Dental & Craniofacial Research (NIDCR) R01 HD081562 / Eunice Kennedy Shriver National Institute of Child Health and Human Development; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) UL1TR001082 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) SNF 310030A-121574; 310030B-138674 / Swiss National Science Foundation; Swiss National Science Foundation (SNSF); European Commission Department of Pediatrics, Children's Hospital Colorado
- Language
- English
- Date published
- 07/15/2016
- Academic Unit
- Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research; Periodontics
- Record Identifier
- 9984284449402771
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