Browsing by Author "Gonzales, Lauren"
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Item Contrast-enhanced micro-CT approaches for visualizing musculoskeletal development in neonatal mice(2023) Stalls, Javan; Miller, Courtney; Gonzales, Lauren; Lesciotto, Kate; Handler, Emma; Organ, Jason; Menegaz, Rachel A.Contrast-enhanced micro-CT approaches for visualizing musculoskeletal development in neonatal mice Javan A. Stalls, Courtney A. Miller, Jason M. Organ, Emma K. Handler, Lauren A. Gonzales, Kate M. Lesciotto, Rachel A. Menegaz Purpose: While there are many forms of radiological imaging that can be used to gather anatomical data from biological specimens, computed tomography (CT) imaging has been the gold standard for visualizing dense tissue, such as bone, with detailed resolution. However, this imaging modality is not well suited for soft tissues (muscle, brain, abdominal organs, cartilage, etc.) due to their decreased tissue density. The inability to distinguish between soft tissues in CT scans limits our ability to investigate the bone-muscle interactions known to stimulate and direct bone modeling during early postnatal development. The development of contrast-enhancing staining agents, capable of binding materials to increase their radiodensity, has allowed for more accurate and enhanced visualizations of less dense soft tissues, such as muscle and brain structures. Contrast agents such as iodine have differential affinities for the different soft tissues in the body allowing for easier visualization and segmentation of soft tissues in relation to the skeleton. Previous studies have used contrast-enhanced CT (CE-CT) scanning to analyze early development of mice from prenatal stages to postnatal day 7. However, additional CE-CT imaging during the first three postnatal weeks is needed to understand muscle-bone interactions during critical periods of behavioral development, such as suckling and weaning. The goal of this project is to develop a CE-CT protocol and corresponding anatomical atlas showing the development of skeletal and soft tissue structures in the crania of neonatal mice from birth to weaning. Methods: Neonatal and preweaning mice (B6C3Fe a/a-Col1a2OIM/J) were euthanized on day of birth (P0), postnatal day 7 (P7), and postnatal day 14 (P14). Ethanol-fixed tissues were submerged in 1.25% iodine in 70% ethanol (I2E) for 2-14 days, with the skin intact in order to preserve cutaneous musculature. Both pre-stained and post-stained tissues were scanned using a MRS CT-80 micro-CT machine (20 µm3 voxel resolution). Results: Preliminary CE-CT scans following 10 days in an iodine stain present improved visualization of soft tissue (brain structures, cranial muscles, salivary glands) when compared to the baseline bone CT scans. Conclusion: These scans will be used to develop 3D models of musculoskeletal ontogeny from birth-weaning, providing insights into this critical developmental period. The use of CT contrast agents such as iodine offers new opportunities to investigate the anatomical interactions of bone and muscle during early development, and can be applied to investigate models of both normal growth and pathological disorders affecting musculoskeletal growth.Item Cranial Bone Ossification Trajectories in a Mouse Model of Osteogenesis Imperfecta(2023) Miller, Courtney; Lugo, Laura; Husain, Tooba S.; Organ, Jason; Handler, Emma; Gonzales, Lauren; Menegaz, Rachel A.Purpose: Osteogenesis imperfecta (OI) is a genetic disorder that affects the production of type I collagen. Altered collagen production results in delayed or impaired skeletal formation and biomineralization. It also results in the defining characteristics of OI: brittle bones and high rates of fractures. Investigations of skeletal growth in OI have primarily focused on the postcranial skeleton, where interrupted, atypical, and disorganized ossification is seen at long bone growth plates. However, few studies have investigated changes in craniofacial growth in OI and there are currently few early interventions to improve growth trajectories in this region. The current medication prescribed for children with OI to improve skeletal growth, such as bisphosphonates, have major side effects and are not suitable for long-term use. A better understanding of craniofacial development in OI can help with targeting specific developmental stages when new treatments can be administered to provide the best results. The aim of this study is to examine cranial ossification from birth to weaning to determine where and when differences in growth occur in OI. We hypothesize that starting at birth mice with OI will have delayed craniofacial growth due to the poor collagen formation. Methods: To test our hypothesis, we collected cranial bone volumes from micro-CT scans of the homozygous recessive OI murine model (OIM or B6C3Fe a/a-Col1a2oim/oim) and compared them to their wild type (WT) littermates. The OIM model has a COL1A2 mutation that has been found to express a similar skeletal phenotype to the severe form (type III) of OI in humans. Bone volumes were collected from birth (P0) and weaning (P21) from the nasal, frontal, parietal, interparietal, and occipital bones (n=2/genotype/timepoint). Results: At birth, OIM and WT bone volumes were similar. By weaning, bone volume was lower in OIM mice compared to WT mice. Our results demonstrate that OIM mice have reduced rates of bone ossification between birth and weaning, and these differences are most profound in the facial and occipital regions. Additionally, OIM skulls are characterized by low bone volume and potential delays in the closure of cranial sutures and fontanelles. Conclusions: This study suggests that the divergence in cranial ossification rates related to COL1A2 mutations occurs postnatally. Interventions to recover craniofacial bone growth in this experimental model should focus on the critical growth period between birth and weaning. Results from this research have the potential to assist in developing treatments and highlight the importance of early life development of the craniofacial bones in human patients with OI.Item CT-based assessment of lower limb surface area, volume, and tissue composition: Implications for ecogeographic rules of thermoregulation(2022-05) Carey, Barclay L.; Maddux, Scott D.; Romero, Steven A.; Gonzales, LaurenAnthropological research into human climatic adaptation has shown that global variation in skin surface-area to body volume ratio is generally consistent with theoretical predictions of ecogeographic rules. NSF has funded a research project in which human subjects will undergo full-body computed tomography scanning, and physiological testing during exposure to climatic extremes, to permit direct evaluation of associations between morphological variation and thermoregulatory physiology. This project entailed the development of analytical methods for the NSF project, which will be used to 1) compare CT-derived SA/V ratios to traditional estimation methods, and 2) to evaluate potential volume differences in internal tissue compositions (e.g., bone, muscle, fat).Item DiGeorge Syndrome in a 32-year-old male: A Cadaver Study(2024-03-21) Chatta, Waleed; Dahl, Kaylee; Findley, Brennan; Flume, Hayden; Miguel, Kristen; Patel, Anjali; Shindler, Sydney; Menegaz, Rachel A.; Gonzales, LaurenBackground: DiGeorge Syndrome (DGS) is one of the most encountered chromosomal syndromes in the population and is marked by the deletion of 22q11.2. Phenotypic expression varies widely between patients. Main features include cardiac and conotruncal abnormalities, craniofacial anomalies including cleft palate, thymic hypoplasia, hypocalcemia, and scoliosis. The branching pattern of the great vessels is known to be highly variable in DGS and a unique manifestation is found in this case. Case Information: This case report examines a 32-year-old deceased male with DGS, and a history of atrial fibrillation, pulmonary atresia-ventricular septal defect, pulmonary artery stenosis, pulmonary hypertension, and six heart surgeries. The cause of death was unspecified natural causes. Initial dissection of the thoracic cavity revealed clear signs of cardiomegaly and a severe scoliotic curve extending to the lumbar region. Further heart dissection revealed sutures and pericardial reconstruction confirming previous surgeries, likely to reconstruct the greater vessels. External findings include an aortic arch variant consisting of absent brachiocephalic trunk, a unique branching pattern of the great vessels directly from the aorta, and the wrapping of the proximal descending aorta around the trachea before descending. Pulmonary trunk adhesion to the heart's surface via scar tissue indicates surgical reconstruction. The left pulmonary artery was significantly constricted while the right pulmonary artery was expanded with immediate branching into smaller segments upon entering the lung, suggesting that more blood was shunted into the right lung. The right atrium appeared significantly enlarged with appropriate size compensations noticed in pectinate muscles and crista terminalis. The right auricle was small and only observable internally. The coronary sinus was abnormally enlarged, comparable in size to the opening of the inferior vena cava. Circular shaped scar tissue on the external surface of the sinus indicates a surgical correction. The right ventricle contained an abnormally enlarged moderator band. Dense scar tissue stenosis was visualized along the pulmonary outflow valve with sutures present along the entire circumference of outflow tract prior to pulmonary artery bifurcation indicating surgical reconstruction. Additional sutures were observed inferior to the circumferential sutures along the wall between the aorta and pulmonary trunk, potentially to seal a prior communicating shunt. The pulmonary veins and left atrium appeared normal; however, possible stenosis of the bicuspid valve was noted but further assessment is needed to confirm. The left ventricle showed enlarged papillary muscles and chordae tendinea which are hypothesized to be a byproduct of the overall increased heart size. The left ventricular wall was twice the thickness of the right ventricular wall, an expected proportion based on heart size and ventricular work. The aortic valves appeared slightly stenosed with cusp buildup. Coronary ostia appeared normal. Conclusion: This cadaveric case study reflects a unique cardiac presentation of DGS within an adult male. With DGS being a rather common chromosomal disorder with highly variable phenotypic expression, there is an importance to explore anatomical variants, their prevalence, and the needed surgical corrections present within patients to ensure that a more comprehensive diagnosis and care plan can be provided in future diagnostic settings.Item Effects of Osteogenesis Imperfecta on Dental Tissue Volumes in Mice(2022) Moore, Jacob; Handler, Emma; Menegaz, Rachel A.; Gonzales, Lauren; Organ, JasonOsteogenesis imperfecta (OI), commonly known as brittle bone disease, is associated with lifelong dental problems, including increased dental fractures, discolored teeth, and malocclusion. OI is a disorder of the type I collagen protein. Insufficient amounts or misshapen forms of this protein lead to disruptions in the microstructure of bone and teeth tissues. Dentin, the hard tissue which comprises the bulk of the tooth and absorbs shock forces during chewing, develops on a type I collagen matrix. Thus, collagen abnormalities in OI lead to disorganized and less stable dentin. Further, teeth in people with OI frequently exhibit dentin hypertrophy, where increased amounts of dentin are deposited at the interior of the tooth, shortly after dental eruption. Enamel, unlike dentin, develops on a matrix of non-collagenous proteins, and is thought to develop normally in OI. However, abnormalities in the underlying dentin in OI can lead to enamel fractures. Finally, the teeth in people with OI have often been noted to be smaller than those of people without OI. Because dental development occurs early in life, there is a lack of data surrounding the developmental processes and associated issues in dental development of children with OI. Mice are commonly used models for dental development, yet, this process has not yet been studied in mice. The objective of this study is to compare dental tissue volumes of teeth from mice with OI (oim) and wild type mice (wt) at different developmental stages to determine the degree of volume and gross dental size differences during late growth stages. Three-dimensional models of upper and lower first molars and incisors were created from microCT scans from oim and wt mice. Scans were taken at weaning age (four weeks after birth; "W4") and young adulthood (sixteen weeks after birth; "W16"). Dental tissue volumes were measured using 3D Slicer and normalized to mandibular centroid size. Mann-Whitney U tests were used to compare tissue volumes between genotypes and age groups. At W4 and W16, oim mice had significantly lower dentin volumes and total tooth volumes for upper incisors than wt mice (p < 0.05), with no significant difference between groups for other tooth types at either timepoint. At W16, total tooth volume was significantly lower in oim mice for molars before adjusting for mandible size (p < 0.05). For both oim and wt groups, W16 mice had significantly greater dentin, enamel, and total tissue volumes for lower and upper incisors compared to W4 mice (p < 0.05), as well as greater dentin volumes for lower molars (p < 0.05). These results demonstrate that the trend of smaller teeth in humans with OI also holds for the oim mouse. These differences are present at both the juvenile and young adult life stages. This affirms the oim mouse as a possible model for dental development in humans with OI. Further studies are needed to determine the developmental program of these volume differences at earlier growth stages.Item Effects of Osteogenesis Imperfecta on the Cochlea and Sensorineural Hearing(2022) Huston, Lila Athena; Menegaz, Rachel A.; Handler, Emma; Organ, Jason; Gonzales, LaurenBackground: Osteogenesis imperfecta (OI), a developmental disorder of type I collagen, is known to cause hearing loss in ~ 60% of the diseased population. Identified forms include conductive hearing loss (17.4% of OI patients), involving loss of function within the ossicular chain, and sensorineural hearing loss (25.8%), resulting from damage to the cochlea, with the most predominant form being mixed hearing loss (56.8%), involving damage to both the cochlea and ossicles. While OI-related pathologies have largely focused on the middle ear, the pathological appearance of the cochlea (the organ most often compromised in OI-related hearing loss) has gained little focus. In this study, we examine OI-related pathologies on the cochlea in a mouse model for the severe type III OI, to document 1) any visible variation between WT and OI variants, and 2) assess the encroachment of the otic capsule onto the cochlea by analyzing differences in duct volumes. We hypothesize that cochlea in mice with OI will have less consistent morphology overall than their WT counterparts due to abnormal growth of the bony capsule. Methods: 16 week old OIM mice (B6C3Fe a/a-Col1a2oim/J) (n=6) were compared to unaffected wildtype (WT) littermates (n=6) with no known hearing defects. High-resolution micro-CT scans were created for all specimens and 3D models and volumes of the cochlea were generated using 3D Slicer software. Two-tailed Mann-Whitney U-tests were used to investigate differences between 1) right and left ears of the same mouse to examine intraindividual symmetry and 2) differences in volumes between WT and OI cochlea. Results: No major morphologic differences between OI and WT were observed, except for minor areas of higher ossification at the base of the cochlea, mostly within the OI sample. Within WT specimens, we observed little intraindividual difference in the cochlear volume (0-3%). Within OI specimens, significant differences were observed in cochlear volume between right and left ears in the same animal (4-15%; p< 0.05), indicating potential unilateral effects. When average WT and OI volumes were compared, there was much overlap between the two samples although the OI volumes had a significantly larger range than the WT range (Mann-Whitney U, p< 0.05). Discussion: Overall, our results indicate that mice with OI are much more likely to have evidence of unilateral cochlear volume losses, despite very little difference in overall shape appearance, possibly due to bony capsule encroachment. This find indicates an extremely high potential for sensorineural and mixed hearing loss in OI-bred mice and elucidates at least one mechanism behind how this type of hearing loss might be occurring. Little is known about the pathological appearance of the cochlea in OI, leading to difficulty in managing hearing loss. Further investigation of the etiology and progression of cochlear pathologies will allow for better outcomes in hearing for those patients afflicted with OI-related hearing loss.Item Identification of ecological, locomotor, and morphological indicators of semi-terrestriality in anthropoid primates.(2024-03-21) Thompson, Indya; Perchalski, Bernadette; Maddux, Scott; Gonzales, LaurenSemi-terrestriality , the utilization of both arboreal and terrestrial environments, is commonly discussed in the primatological literature but inconsistently defined, limiting its study in fossil taxa. This project aims to fill that gap by investigating the ecological, morphological and locomotor variables that characterize semi-terrestrial taxa. 18 semi-terrestrial and 17 arboreal anthropoid taxa were identified from the literature. Ecological data were collected from mammalian demographic and environmental databases; postcranial measurements and behavioral data were collected from the literature. Three stepwise canonical variate analyses (CVA) were run (ecological, locomotor, and morphological) to identify factors that discriminate between semi-terrestrial and arboreal primates. The ecological CVA retained population size, social group size, and percentage of leaves in the diet as variables. CV1 (55.8%) differentiated semi-terrestrial platyrrhines from arboreal and semi-terrestrial catarrhines. CV2 (26.9%) distinguished semi-terrestrial platyrrhines and catarrhines cluster away from their arboreal counterparts. The behavioral CVA retained bridging, leaping, quadrupedal walking, climbing, scrambling/clambering and bimanual suspension as variables. CV1 (62.3%) separated semi-terrestrial platyrrhines from semi-terrestrial catarrhines, while CV2 (31.5%) distinguished both semi-terrestrial taxa from arboreal taxa. The morphological CVA did not retain any size-corrected variables, with no iteration of relative long bone lengths differentiating between any of the groups. These results indicate select ecological and locomotor variables can reliably identify semi-terrestrial taxa, helping to improve our understanding of this enigmatic behavior. Future studies should likely include measures of specific bony features to more fully investigate potential morphological indicators of semi-terrestrial behaviors.Item Masticatory muscle morphology in early postnatal mice with osteogenesis imperfecta(2024-03-21) Ansari, Zahra; Miller, Courtney; Emmanuel, Tanusha; Handler, Emma; Gonzales, Lauren; Organ, Jason; Menegaz, Rachel A.Purpose: Osteogenesis imperfecta (OI) is a connective tissue disorder resulting from mutations in COL1A1 or COL1A2, responsible for encoding type I collagen alpha chains. While OI is primarily distinguished by manifestations of bone fragility, including recurrent fractures and bone deformities, muscle abnormalities have also been documented in those affected by OI. While prior research has shown postcranial muscle weakness in mouse models of OI, it remains unclear whether this also applies to feeding musculature and if these differences are present at birth or develop postnatally. This study investigates the development of the masticatory muscles during the early postnatal period in a mouse model. Our hypothesis posits that mice affected by OI will exhibit decreased muscle mass, and therefore potentially weaker muscles, in comparison to unaffected mice. Methods: Cranial tissues from OIM mice (B6C3Fe a/a-Col1a2oim/J) and unaffected wild type (WT) littermates were collected at day of birth (P0) and postnatal day 14 (P14). Tissues were fixed and stained with 1.25% buffered Lugol’s solution, then micro-CT scanned with a reconstruction of 0.02 mm3 voxels. 3D Slicer software was used to isolate and measure the volumes of the superficial masseter, deep masseter, and temporalis muscles. Muscle volumes were compared between genotypes using a Mann-Whitney U test. Results: At birth, no significant differences were observed in body mass or muscle volumes between OIM and WT mice. A trend was observed for OIM mice to have lower superficial masseter volumes compared to WT mice at P0, but this difference was not significant. At P14, OIM mice have significantly lower body weights (p=0.002). Data collection is ongoing for volumetric muscle data from the P14 stage. After birth, body masses diverge rapidly between OIM and WT mice. These growth curves suggest poor feeding performance during the suckling stage in OIM mice. Although masticatory muscle volumes (similar to body mass) start out similar between genotypes at birth, a trend for decreased superficial masseter volume in OIM mice suggests feeding musculature will also lag behind unaffected mice during early postnatal growth. Conclusion: The production of strain above an osteogenic threshold by feeding musculature is critical to typical craniofacial growth during early life. Weaker masticatory muscles may produce lower (yet still osteogenic) levels of strain, contributing to the midfacial hypoplasia seen in OIM mice. A better understanding of muscle development during this critical growth period will provide insight on feeding disorders seen in OI, and the development of the craniofacial phenotype in pediatric patients with OI.Item Neurocranial Growth in the OIM Mouse Model of Osteogenesis Imperfecta(2022) Husain, Tooba S.; Miller, Courtney; Steele, Ashley T.; Gonzales, Lauren; Handler, Emma; Organ, Jason; Menegaz, Rachel A.Osteogenesis imperfecta (OI) is a disorder of type I collagen characterized by abnormal bone formation and weakened bone architecture. Human patients with OI have larger cranial vaults (macrocephaly), altered cranial base morphology including basilar invagination and platybasia (skull base flattening), and midfacial underdevelopment. The neurocranial changes may affect both underlying nervous tissue and growth patterns of the facial skeleton. However, we still do not fully understand how and when these divergent morphologies occur. The aims of this study are: (1) to investigate the integrated development of the skull and the brain in amouse model of OI; and (2) to identify the developmental trajectories of these structures to facilitate future therapeutic interventions. We hypothesize that compared to unaffected mice, mice with OI will have decreased brain volumes due to an overall reduction in cranial size and decreased cranial base angles (CBA) due to platybasia. To test these hypotheses, we used the osteogenesis imperfecta murine (OIM or B6C3FE a/a-Col1a2/J), a model for the severe type III OI in humans, and unaffected wild-type (WT) littermates. Mice were imaged using in vivo micro-computed tomography (micro-CT) at the juvenile (week 4; 10 OIM/14 WT) and adult (week 16; 9OIM/11 WT) stages. All measurements were taken in 3D Slicer software. 82 cranial landmarks were used to calculate centroid size, an estimate of overall head size. The segmentations tool was used to create virtual endocasts as a proxy for brain volume. The angle tool was used to measure CBA in the midsagittal plane using threelandmarks: foramen cecum, midsphenoidal synchondrosis, and basion. Mann-Whitney U tests were used to compare centroid sizes, brain volumes, and CBA between the genotypes. Both juvenile (p=0.008) and adult (p=0.003) OIM mice were found to have absolutely smaller brains than WT mice. However, OIM mice also have significantly smaller cranial centroid sizes compared to WT mice (p=0.003, p< 0.001). When scaled to cranial size, juvenile mice had relatively larger brain volumes (p=0.016) butadult OIM relative brain volumes were not significantly different from WT. No significant difference was seen in CBA at the juvenile (p=0.065) or adult (p=0.171) stages, however a trend was observed for decreased CBA at the adult stage. These results suggest that neurocranial dysmorphologies in OI may be more severe at earlier stages of postnatal development. Previous analyses of these mice have documented relative skeletal macrocephaly in both juvenile and adults, however here we document an increase in relative endocranial volume only at the juvenile stage. A reduction in CBA during growth, possibly due to platybasia, may underlie this decoupling between external and internal cranial morphology. Future work will investigate the effect of CBA on facial growth and midfacial underdevelopment in these mice. A better understanding of the integration and growth trajectory of the neurocranium is foundational for formulating treatments to manage basicranial instabilities in patients with OI. Support or Funding Information Funding was provided by an Indiana University Collaborative Research Grant, Ralph W. and Grace Showalter Trust, and a UNTHSC Physiology & Anatomy SEED Grant.Item Osteogenesis Imperfecta: Implications of Using Micro-CT for Visualizing Developmental Variation in the Middle and Inner Ear of OIM Mice(2023) Judd, Dallin; Stucki, Brenton; Miller, Courtney; Handler, Emma; Menegaz, Rachel A.; Gonzales, LaurenOsteogenesis Imperfecta: Implications of Using Micro-CT for Visualizing Developmental Variation in the Middle and Inner Ear of OIM Mice Dallin R. Judd1, Brenton R. Stucki1, Courtney A. Miller2, Emma Handler3, Rachel A. Menegaz2, Lauren A. Gonzales2 1 Texas College of Osteopathic Medicine, University of North Texas Health Science Center, TX 2 Department of Physiology and Anatomy, University of North Texas Health Science Center, TX 3 Department of Anatomy and Cell Biology, University of Iowa, IA Osteogenesis imperfecta (OI), also known as brittle bone disease, is a genetic bone disorder caused by mutations in the genes COL1A1 and COL1A2, which are responsible for encoding type I collagen. Much is known regarding the effects of the disease on cranial and postcranial elements. However, little is known regarding the pathogenesis and physical manifestations of OI in the ear despite the high rates of hearing loss in patients with OI (~60% of the population is affected). Because ossification or demineralization of structures in the ear may affect the efficacy of certain treatments like cochlear implants, this information deficit limits the treatment options available for OI patients. Thus, the purpose of our research is to visualize and document anatomic variation in the ears of mice bred to have the Type III OI genetic variant in order to better understand the cause of OI-related hearing loss. 3D models of the middle and inner ears were created from micro-CT scans that also employed two new contrast-enhanced methods to visualize the cochlea and middle ear (malleus, incus, and stapes). All CT scanning were done on the UNTHSC campus using the new Small Animal Imaging Facility (SAIF) as part of a previous study. The scan resolution was approximately 20μm. The studied WT and OIM mouse samples include three time points intended to capture a developmental sequence: 0-day-old (WT=20, OIM=29), 7-day-old (WT=23, OIM=23), and 14-day-old mice (WT=22, OIM=18). The visualization software Avizo was then used to digitally segment the bone of the inner ear and middle ear. Gross anatomic differences are currently being documented for each region. Previous work has shown higher levels of ossification and marked bony encroachment of the otic capsule onto the cochlea in the adult OIM mouse model, potentially damaging the soft tissue of the membranous labyrinth. This research uses micro-CT imaging designed to capture a developmental sequence, giving us the potential to elucidate how and when the bony intrusions are impacting surrounding structures. Insight into this anatomical damage may help further clarify OI-related pathology, including the distinction between hearing loss associated with the middle ear (conductive hearing loss) vs. hearing loss associated with the inner ear (sensorineural hearing loss). Furthermore, a preliminary analysis of the developmental sequence should provide insight into when these anatomical changes are first occurring. Upon completion, this research will demonstrate the efficacy of using these new imaging approaches for studying minute structures of the ear and may markedly advance our understanding of the pathogenesis of OI-related hearing loss.Item Pre-weaning craniofacial development in mice with Osteogenesis Imperfecta(2024-03-21) Miller, Courtney; Emmanuel, Tanusha; Gonzales, Lauren; Handler, Emma; Organ, Jason; Menegaz, Rachel A.The craniofacial region plays a pivotal role in various physiological functions, including mastication, speech, and respiration. Early life behaviors have a profound role in shaping adult structure and function. In the early stages of life, all mammals undergo the 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 overall quality of life. This study investigates the preweaning craniofacial growth trajectory in mice OI (the OIM mouse) compared to unaffected wild type (WT mice). We hypothesize that mice with OI will exhibit smaller overall size and greater craniofacial variation than WT mice due to the abnormal collagen synthesis during skull development. Micro-CT based geometric morphometric analyses of the OIM mouse model (B6C3Fe a/a-Col1a2oim/J) were used to compare craniofacial size and shape differences at birth (P0; n=27 OIM / 20 WT) and postnatal days 7 (P7; n=21/21) and 14 (P14; n=16/20). The SlicerMorph package for 3D Slicer software was used to generate landmark point clouds for the cranium and mandible. Dimension ratios were calculated as width/length for the crania. Principal component analysis with Procrustes ANOVA were used to examine differences between genotypes at each time point, and a canonical variate analysis (CVA) used to identify shape features that maximize the distinction between genotypes across all time points. Results reveal the development of significant differences in both shape and size between the genotypes following birth. At birth, size and shape are similar between genotypes. However, by P7 and P14, OIM mice are significantly (p<0.05) smaller and display pronounced shape changes (p<0.001) characterized by larger neurocranium and shorter viscerocranium. Additionally, OIM mice have significant mandibular alterations by P7 (p<0.001) - shorter ramus, more posterior position of the coronoid, and shorter and wider dental arcade. All of these changes align with the suckling developmental stage, suggesting changes in the ratio of growth between the neurocranium and the viscerocranium during early life. Widening the neurocranium while shortening the viscerocranium during this critical developmental stage alters the masticatory muscle line of action, consequently, influences the health of individuals with OI. These findings underscore the suckling stage’s significance in shaping the foundational structures for later life, providing insights into OI craniofacial development, and suggest potential benefits to directing interventions toward an earlier time point for more effective treatment of OI.Item SPHARM, a New Computational Approach for Locomotor Signal Identification in 15 MYA fossil primates from Maboko Island, Kenya(2023) Thompson, Indya; Arney, Irisa; Perchalski, Bernadette; Ratkowski, Jakub; Benefit, Brenda; McCrossin, Monte; Gonzales, LaurenPurpose: Maboko Island, western Kenya preserves a diverse collection of seven catarrhine proximal humeri from the middle Miocene (~15 Ma). Proximal humeri are extremely rare in the Miocene (25-5 mya), limited to only four specimens outside of Maboko. Identified taxa include cercopithecoids (Victoriapithecus), nyanzapithecines (Mabokopithecus), small-bodied "apes” ("Micropithecus”), and large-bodied hominoids (Kenyapithecus), all of which provide important insight into diversity of locomotor patterns among middle Miocene catarrhines. Methods: This project uses weighted spherical harmonics analysis (SPHARM), a landmark-free automated method to explore locomotor signals in the Maboko sample. Meshes of five intact humeri were compared to a sample of 94 extant catarrhines and platyrrhines, spanning a range of locomotor modes (suspensory arborealism, terrestrial quadrupedalism, arboreal quadrupedalism, and knuckle walking). Principal components analyses (PCA) were run on the associated SPHARM coefficients to explore differences among these locomotor groups. Results: Preliminary assessment shows extant suspensory arboreal primates clustering away from both knuckle-walking and quadrupedal group along PC1 and PC2. Along PC2, further separation was observed between arboreal and terrestrial quadrupeds. The Maboko specimens show distinctions between all five of the fossil primates, particularly between two taxa previously suggested to be arboreal (Mabokopithecus and "Micropithecus”) and two taxa documented as terrestrial quadrupeds (Victoriapithecus and Kenyapithecus). Conclusion: Though preliminary, this analysis provides insight into the diversity of catarrhine locomotor behavior during the middle Miocene, reinforcing previous descriptions of locomotor partitioning among the Maboko specimens. Future research that includes early and late Miocene taxa may shed light into diversity of catarrhine locomotor behaviors that spanned the Miocene epoch.