Embryonic inhibition of colony‐stimulating factor 1 receptor impacts craniofacial morphogenesis

Embryonic inhibition of colony‐stimulating factor 1 receptor impacts craniofacial morphogenesis

Objectives Colony‐stimulating factor‐1 receptor (CSF1R) is vital for the recruitment of monocytes, and their proliferation and differentiation into functional osteoclasts. Mouse studies, where CSF1R and its cognate ligand are absent, have significant craniofacial phenotypes, but these have not been...

Full description

Saved in:
Bibliographic Details
Published in:Orthodontics & craniofacial research Vol. 26; no. S1; pp. 20 - 28
Main Authors: Nagra, Ashina, Katsube, Motoki, Gao, Wade, Rosin, Jessica M., Vora, Siddharth R.
Format: Journal Article
Language:English
Published: England Wiley Subscription Services, Inc 01-12-2023
Subjects:
Animals
Computed tomography
craniofacial morphogenesis
CSF1R
Dental caries
embryonic development
Embryos
Female
geometric morphometrics
Immunofluorescence
Jaw
Juveniles
Macrophage Colony-Stimulating Factor - pharmacology
Mandible
Mandible - metabolism
Mice
Monocytes
Morphogenesis
Osteoclastogenesis
Osteoclasts
Phenotypes
Pregnancy
Skull
Skull - diagnostic imaging
Skull - metabolism
X-Ray Microtomography
CSF1R
craniofacial morphogenesis
embryonic development
geometric morphometrics
osteoclasts
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Objectives Colony‐stimulating factor‐1 receptor (CSF1R) is vital for the recruitment of monocytes, and their proliferation and differentiation into functional osteoclasts. Mouse studies, where CSF1R and its cognate ligand are absent, have significant craniofacial phenotypes, but these have not been studied in detail. Materials and Methods Pregnant CD1 mice were fed diets laced with CSF1R inhibitor—PLX5622 starting at embryonic day 3.5 (E3.5) up to birth. Pups were collected at E18.5 to study CSF1R expression using immunofluorescence. Additional pups were studied at postnatal day 21 (P21) and P28 using microcomputed tomography (μCT) and Geometric Morphometrics, to evaluate craniofacial form. Results CSF1R‐positive cells were present throughout the developing craniofacial region, including the jaw bones, surrounding teeth, tongue, nasal cavities, brain, cranial vault and base regions. Animals exposed to the CSF1R inhibitor in utero had severe depletion of CSF1R‐positive cells at E18.5 and had significant differences in craniofacial form (size and shape) at postnatal timepoints. Centroid sizes for the mandibular and cranio‐maxillary regions were significantly smaller in CSF1R‐inhibited animals. Proportionally, these animals had a domed skull, with taller and wider cranial vaults and shortening of their midfacial regions. Mandibles were smaller vertically and anterio‐posteriorly, with proportionally wider inter‐condylar distances. Conclusions Embryonic inhibition of CSF1R impacts postnatal craniofacial morphogenesis, with significant influences on the mandibular and cranioskeletal size and shape. These data indicate that CSF1R plays a role in early cranio‐skeletal patterning, likely through osteoclast depletion.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1601-6335
1601-6343
DOI:10.1111/ocr.12671