Pattern formation ensures that tissues, organs, and structures develop in the correct place and orientation within the body. Patterning processes are at the heart of morphogenesis yet remain poorly understood due to their complexity. The sea urchin larval skeleton provides a simple model to study skeletal patterning, where the skeleton-producing primary mesenchyme cells (PMCs) receive patterning cues from the overlying ectoderm. The normal skeletal patterning process requires the PMCs to migrate within the blastocoel to specific positions. While ectodermal and endodermal signals regulate PMC positioning and differentiation, additional signals act to regulate biomineralization per se in the PMCs. However, the distinction between these effects is not well understood and new efforts have been made to identify these patterning and biomineralization cues that regulate sea urchin skeletal development. Understanding the mechanism by which PMCs interpret and transduce patterning cues into a migratory bias and/or positional information will provide insight into tissue patterning and developmental plasticity both in sea urchins and, more broadly, in deuterostomes. Ethanol is a known vertebrate teratogen that causes craniofacial defects as a component of fetal alcohol syndrome. Perturbations to retinoic acid biosynthesis and the Hedgehog signaling pathway are thought to be causal for the fetal alcohol syndrome phenotype in vertebrates. We used the sea urchin embryo to gain evolutionary insight into how ethanol affects embryonic development in a basal deuterostome animal. We found that ethanol specifically perturbs skeletal patterning. When sea urchin embryos are exposed to ethanol, they exhibit conspicuously delayed development, and broad skeletal patterning defects that are potentially analogous to fetal alcohol syndrome associated facial patterning defects in vertebrates and humans. PMC transplantation experiments demonstrated that ethanol-induced defects are not specific to the PMCs, and instead reflect the perturbation of patterning cues. We also found that the expression of both patterning cues and PMC-specific genes was delayed by ethanol exposure. Surprisingly, our results indicate that retinoic acid and Hedgehog pathways are not functionally relevant for the teratogenic effects of ethanol in the larval skeletal patterning process, indicating a lack of evolutionary conservation of these pathways in ethanol-mediated teratogenesis among deuterostomes. Temporal transcriptome analysis revealed significant impacts of ethanol on signaling and metabolic gene expression and a disruption in the timing of expression for sea urchin specification gene regulatory network (GRN) genes. Surprisingly, multiple circuits with the GRN exhibit precocious expression while others are delayed. Taken together, our results suggest that the skeletal patterning perturbations in ethanol-treated sea urchin embryos arise from a loss of temporal synchrony within and between the instructive and responsive tissues during pattern formation.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/47760 |
| Date | 27 November 2023 |
| Creators | Rodriguez-Sastre, Nahomie |
| Contributors | Bradham, Cynthia A. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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