Knockout of the gene encoding the extracellular matrix protein SNED1 results in early neonatal lethality and craniofacial malformations
Name
Barque et al Prepub final reduced.pdf
Description
Accepted version
Size
12.37 MB
Format
Adobe PDF
Checksum (MD5)
930de72b653cc21db713989c0f3f218e
Author(s)
Barqué, Anna
Jan, Kyleen
De La Fuente, Emanuel
Nicholas, Christina L.
Hynes, Richard O
Naba, Alexandra
Date Issued
October 2020
Journal
Developmental Dynamics
Publisher
Wiley
Citation
Barqué, Anna et al. "Knockout of the gene encoding the extracellular matrix protein SNED1 results in early neonatal lethality and craniofacial malformations." Developmental Dynamics 250, 2 (October 2020): 274-294. © 2020 American Association of Anatomists
Version
Author's final manuscript
Abstract
Background: The extracellular matrix (ECM) is a fundamental component of multicellular organisms that orchestrates developmental processes and controls cell and tissue organization. We previously identified the novel ECM protein SNED1 as a promoter of breast cancer metastasis and showed that its level of expression negatively correlated with breast cancer patient survival. Here, we sought to identify the roles of SNED1 during murine development. Results: We generated two novel Sned1 knockout mouse strains and showed that Sned1 is essential since homozygous ablation of the gene led to early neonatal lethality. Phenotypic analysis of the surviving knockout mice revealed a role for SNED1 in the development of craniofacial and skeletal structures since Sned1 knockout resulted in growth defects, nasal cavity occlusion, and craniofacial malformations. Sned1 is widely expressed in embryos, notably by cell populations undergoing epithelial-to-mesenchymal transition, such as the neural crest cells. We further show that mice with a neural-crest-cell-specific deletion of Sned1 survive, but display facial anomalies partly phenocopying the global knockout mice. Conclusions: Our results demonstrate requisite roles for SNED1 during development and neonatal survival. Importantly, the deletion of 2q37.3 in humans, a region that includes the SNED1 locus, has been associated with facial dysmorphism and short stature.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/dvdy.258
