Browsing by Subject "Mesoderm"

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    Fibronectin and Laminin, extracellular matrix proteins, have an origin in mesoderm tissue and promote anterior neural tube closure in zebrafish
    (2023-05) Olson, Kirsta
    The neural tube, the precursor to the vertebrate central nervous system, forms through the process of neurulation. During neurulation, a flat neural plate folds and the lateral edges bind to form a closed tube. Failure of neurulation results in neural tube defects (NTD). In humans, NTD causes life-threatening birth defects such as anencephaly, spina bifida, and craniorachischisis. Work from several laboratories has demonstrated that mesoderm is required for anterior neural tube closure in mice and zebrafish. In all vertebrates, there is an extracellular matrix between the mesoderm and the developing neural tube. I hypothesized Fibronectin (Fn) and Laminin (Lam), extracellular matrix proteins, have an origin in mesoderm tissue and promote anterior neural tube closure. Supporting my hypothesis, the mRNA for extracellular matrix genes lama1, lama2, lamb1a, lamc1, fn1a, and fn1b were all expressed in mesoderm tissue adjacent to the developing neural tube. Further, expression of these lam and fn genes in the mesoderm occurred during neurulation. This suggests that one role of mesoderm in neural tube closure is to contribute to the extracellular matrix that surrounds the developing neural tube. Consistent with this and supporting my hypothesis, an extracellular matrix is required for neural tube closure in zebrafish. Loss of either lamc1 or fn1a alone resulted in a closed anterior neural tube. In contrast, approximately 50% of lamc1 ; fn1a double mutants had an open forebrain neural tube. In the midbrain, some of the embryos deficient in lamc1 ; fn1a had a double roof plate phenotype. In the hindbrain of wildtype embryos, ephrin receptor A4a (ephA4a) is expressed in rhombomeres 1, 3, and 5. Interestingly, most lamc1 ; fn1a double mutants had ephA4a expression in all three rhombomeres, but a small subset displayed a “twisted brain” phenotype that is also present in embryos with severe loss of mesoderm and an open anterior neural tube. This project provides additional connections among the mesoderm, the extracellular matrix, and neurulation.
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    The role of endoglin during mesoderm specification
    (2015-05) Baik, June
    Embryogenesis requires spatiotemporally regulated cellular signals and gene expressions that influence lineage specification, progenitor patterning, and morphogenesis. However the molecular mechanisms that explain how the progenitors commit into different lineages are still poorly understood. Endoglin (ENG) is an ancillary receptor for transforming growth factor-beta (TGF-β) and lack of ENG leads impaired hematopoiesis, cardiac defects and embryonic lethality. Considering the fact that certain mesodermal population can give rise to both cardiac and hematopoietic cells, it indicates that endoglin may play a role in these cell types. Thereby during my predoctoral training, I have aimed to elucidate how endoglin regulates the cell fate choice that results in the specification of early mesodermal precursors into the cardiac or hematopoietic cells. In Chaper 2, I demonstrate that ENG promotes the commitment of early mesodermal progenitors to the hematopoietic lineage at the expense of the cardiac cell fate and ENG-mediated hematopoietic commitment occurs through BMP signaling pathway. In Chapter 3, I illustrate the mechanistic insights how ENG, through activation of BMP and WNT signals, regulates the cell fate decision to secure mesoderm commitment towards the hematopoietic lineage. These studies will uncover a novel role of ENG as a potential mediator between BMP and WNT signaling during mesoderm specification and contribute to broaden our understanding of TGF-β signaling in cell fate decision.