Developmental Biology Commons^™

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

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Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Connecting Genotype And Phenotype: Investigating The Functional Morphology And Molecular Architecture That Influences Craniofacial Divergence Using Lake Malawi Cichlid Fishes, Leah Delorenzo

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Connecting genotype and phenotype to better understand how species evolve has been a goal of evolutionary developmental biologists over the last 50 years. This dissertation aims to connect genotype and phenotype of the craniofacial skeleton within the adaptive radiation of Lake Malawi cichlids to fortify our understanding of the functional, genetic, and epigenetic factors that contribute to craniofacial divergence. I start with a functional approach using 2D geometric morphometrics to assess craniofacial shape across the Lake Malawi cichlid radiation to bolster our knowledge of the bone phenotypes that are important to niche specialization and are functionally relevant. Next, I use …

Mirna Regulation Of Skeletal Muscle Hypertrophy, Maslyn Greene

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Muscle tissue is vital to animal survival and economically essential to livestock producers. Reduced muscle growth can occur from various reasons, including genetics, nutrition, and the pre and postnatal environment. Understanding the mechanisms behind muscle growth can aid in developing strategies to increase muscle mass. Several methods to increase muscle mass in livestock animals are currently being pursued, including nutrition, hormonal therapy, and genetic selection. One newly developing avenue is using miRNA technologies to change the expression of protein-coding genes. miRNA are a type of RNA that regulate over half of protein-coding gene expression. Here we evaluate muscle characteristics such …

Developmental Effects Of Chronic Low-Level Arsenic Exposure In Mouse Embryonic Stem Cells And In Human Induced Pluripotent Stem Cells, M. Chiara Perego

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Arsenic is an environmental contaminant commonly found in food and drinking water. Exposure to arsenic during embryonic development has been linked to reduced muscle growth, disrupted muscle development and locomotor activity, impaired neurodevelopment, reduced IQ, impaired memory and learning deficits. While the mechanisms responsible for developmental changes following in utero exposure to arsenic are not well known, one possibility is that arsenic might disrupt proper cellular differentiation. Therefore, we aimed to investigate the mechanisms by which arsenic exposure could alter stem cell differentiation into neurons.

First, we continuously exposed P19 mouse embryonic stem (ES) cells to 0.1 μM (7.5 ppb) …

A Novel Gain Of Function Of The Irx1 And Irx2 Genes Disrupts Axis Elongation In The Araucana Rumpless Chicken, Nowlan Freese

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Caudal dysplasia describes a range of developmental disorders that affect normal development of the lumbar spinal column, sacrum and pelvis. An important goal of the congenital malformation field is to identify the genetic mechanisms leading to caudal deformities.
To identify the genetic cause(s) and subsequent molecular mechanisms I turned to an animal model, the rumpless Araucana chicken breed. Araucana fail to form vertebrae beyond the level of the hips. I performed a genome wide association study to identify candidate genomic regions associated with the rumpless phenotype, compared to tailed Araucana. A candidate region of chromosome 2 containing just two genes, …

Early Skeletal Morphogenesis: The Role Of Pharyngeal Endoderm Derived Signaling During Specification Of Craniofacial Skeleton And Interplay Of Mechanical Forces And Molecular Signaling During Skeletal Condensation, Poulomi Ray

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This study examines the fundamental principles governing the early
stages of skeletal morphogenesis. I specifically investigate the specification of mesenchymal progenitor cells to a skeletal fate. Using explant culture system, I determine that the pharyngeal endoderm was sufficient, but not necessary for specifying pre-chondrogenic identity. FGF signaling is both sufficient and required for specification of Sox9 expression and specification of prechondrogenic identity, as demonstrated by the addition of recombinant FGF protein or the FGF receptor inhibitor (SU5402) to explanted tissue, respectively. However, FGF signaling cannot maintain Sox9 expression or initiate the chondrogenic program as indicated by the absence of Col2a1 …

Specification Of The Neural Crest-Derived Pharyngeal Mesenchyme: The Role Of Pharyngeal Endoderm, Fgf And Bmp Signaling In The Establishment Of Prechondrogenic Identity And Initiation Of Chondrogenesis., Megha Kumar

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This study investigates the role of pharyngeal endoderm in the specification of prechondrogenic identity and initiation of chondrogenesis in the proximal mesenchyme of the second pharyngeal arch. The results show that pharyngeal endoderm is sufficient but not necessary for specification of prechondrogenic identity in the cranial neural crest derived arch mesenchyme. A number of Fgf genes - Fgf3, 4, 8 and 19 are expressed in the pharyngeal endoderm. Further, FGF signaling is sufficient and required for the specification of prechondrogenic identity, marked by Sox9 expression. However, FGF signaling is unable to maintain the Sox9 expression and initiate the chondrogenic program. …