Gestational inhibition of CSF1R signaling using PLX5622 drives musculoskeletal changes in postnatal offspring

Area of Science:

• Developmental Biology
• Musculoskeletal Biology
• Craniofacial Biology

Background:

• The interplay between muscle and bone development during gestation is not fully understood.
• Macrophage and osteoclast roles in embryonic development are critical for skeletal formation.
• Gestational perturbations can impact fetal musculoskeletal growth.

Purpose of the Study:

• To investigate the effects of inhibiting colony-stimulating factor-1 receptor (CSF1R) during embryogenesis on craniofacial and mandibular development.
• To analyze the impact of prenatal CSF1R inhibition on the musculature of mastication and tongue.
• To understand the consequences of disrupted macrophage and osteoclast activity on musculoskeletal morphogenesis.

Main Methods:

• Utilized the CSF1R inhibitor PLX5622 in an embryonic mouse model.
• Employed high-resolution microcomputed tomography (μCT) for skeletal analysis.
• Applied geometric morphometric (GM) analysis and dense correspondence analysis (DeCA) for morphological and muscular assessments.

Main Results:

• Significant disruptions in cranioskeletal and mandibular size and shape were observed.
• Prenatal CSF1R inhibition led to notable changes in the morphology of mastication and tongue muscles.
• The study provides direct evidence of altered musculoskeletal development due to in utero CSF1R inhibition.

Conclusions:

• Inhibition of CSF1R signaling during embryogenesis profoundly impacts craniofacial bone and muscle development.
• Prenatal disruption of macrophage and osteoclast function has lasting effects on musculoskeletal morphogenesis.
• This research highlights the critical role of CSF1R signaling in coordinated craniofacial development.