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At birth, mammals experience a massive colonization by microorganisms. We previously reported that newborn mice gestated and born germ-free (GF) have increased microglial labeling and alterations in developmental neuronal cell death in the hippocampus and hypothalamus, as well as greater forebrain volume and body weight when compared to conventionally colonized (CC) mice. To test whether these effects are solely due to differences in postnatal microbial exposure, or instead may be programmedin utero, we cross-fostered GF newborns immediately after birth to CC dams (GF→CC) and compared them to offspring fostered within the same microbiota status (CC→CC, GF→GF). Because key developmental events (including microglial colonization and neuronal cell death) shape the brain during the first postnatal week, we collected brains on postnatal day (P) 7. To track gut bacterial colonization, colonic content was also collected and subjected to 16S rRNA qPCR and Illumina sequencing. In the brains of GF→GF mice, we replicated most of the effects seen previously in GF mice. Interestingly, the GF brain phenotype persisted in GF→CC offspring for almost all measures. In contrast, total bacterial load did not differ between the CC→CC and GF→CC groups on P7, and bacterial community composition was also very similar, with a few exceptions. Thus, GF→CC offspring had altered brain development during at least the first 7 days after birth despite a largely normal microbiota. This suggests that prenatal influences of gestating in an altered microbial environment programs neonatal brain development.
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Early life functional transitions impact craniofacial morphology in osteogenesis imperfecta
Abstract Early life behaviors have a profound role in shaping adult craniofacial morphology. During early life, all mammals undergo the dynamic transition from suckling to mastication, a period coinciding with rapid cranial biomineralization. Osteogenesis imperfecta (OI), a genetic disorder that impacts the production of type I collagen, disrupts biomineralization, leading to craniofacial growth differences affecting quality of life. This study investigates craniofacial development during infant oral motor developmental stages in OI mice compared to unaffected wild‐type littermates (WT mice). We hypothesize OI mice will exhibit smaller overall size, and the adult OI phenotype will develop postnatally in response to masticatory loading. Point cloud and fixed landmarks were collected from micro‐computed tomography scans, then geometric morphometric analyses and interlandmark distances (ILDs) compared craniofacial size and shape between OI and WT mice at birth (P0;n = 27 OI murine/20 WT) and postnatal Days 7 (P7;n = 21/21), 14 (P14;n = 16/20), 21 (P21;n = 20/26), and 28 (P28;n = 26/33). This study found no size and shape differences between genotypes at birth. Starting at P7, OI mice are significantly (p < 0.05) smaller and display pronounced shape changes (p < 0.001) characterized by a larger neurocranium and a shorter viscerocranium. At P21, significant differences emerge in cranial base orientation, neurocranial width, viscerocranial shortening, and zygomatic arch displacement. These findings underscore the importance of early life oral motor stages in developing the adult OI craniofacial phenotype and oral health, suggesting earlier craniofacial interventions may improve effective treatment of OI.
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- Award ID(s):
- 2236027
- PAR ID:
- 10573619
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- The Anatomical Record
- ISSN:
- 1932-8486
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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