We still know very little about the mechanisms that regulate and synchronize morphogenetic events duringlater stages of vertebrate development. Nonetheless, understanding the factors controlling these laterdevelopmental periods is essential to understanding how adult traits form, and will lend insight intomorphological defects and disorders that arise during human post-embryonic fetal and neonatal periods. Thisresearch utilizes the zebra?sh, which undergoes extensive post-embryonic development involvingmodi?cations and maturation in many different organ systems; many of these changes are similar or identicalto processes that occur following embryogenesis in humans. This proposal employs several strategies towardsunderstanding the mechanisms underlying the zebra?sh transformation from larva to juvenile. The ?rst aimadopts a targeted approach, testing the speci?c roles of thyroid hormone in post-embryonic developmentaltransitions. Multiple lines of evidence indicate that thyroid hormone is involved in several developmentalprocesses in zebra?sh, but the ability of this hormone to effect speci?c morphogenetic processes and cellularbehaviors remains unclear.
This aim will test roles of thyroid hormone in promoting both global somaticdevelopmental progression and the behaviors of a speci?c, well-characterized cell lineage that produces adultpigmentation during the larval-to-juvenile transition.
The second aim takes a forward genetic strategy to identifynovel genes required for post-embryonic stage transitions. This approach has already identi?ed two mutantsthat exhibit complete somatic arrest during larval development, ceasing ontogenetic progression at stagesnormally reached by 2- and 3-week old wild-type larvae. These phenotypes suggest an impairment of genesabsolutely required for post-embryonic progression. Mapping and cloning the mutations and characterizing thepathways to which they belong will reveal mechanisms essential for post-embryonic developmental processes;continuation of this screen will identify further larval arrest phenotypes. The ?nal aim utilizes a species relatedto zebra?sh that exhibits a natural failure to execute the terminal stages of somatic post-embryonicdevelopment. Focusing primarily on the structure and expression within the skin, changes in genetic anddevelopmental architecture will be elucidated in this context of post-embryonic developmental truncation.These analyses will reveal the both extent of decoupling between traits and regulatory pathways, and whetherdormant genetic pathways retain responsiveness to a key endocrine mediator of post-embryonic development.Overall, these efforts will characterize the morphogenetic roles of a known endocrine regulator, will identifynovel factors that regulate normal post-embryonic progression, and will establish a novel model for dissectingthe ways in which developmental genetic pathways and endocrine mechanisms can evolve. Moreover, thisproject will complete the developmental biology and genetics training of a scholar with a background inpopulation ecology, and will establish establish the foundation for her independent research laboratory.
The larval-to-adult transformation in zebra?sh includes many processes similar or identical to those occurringin human embryonic; fetal and neonatal development; despite clear biomedical relevance; we know very littleabout the mechanisms controlling and synchronizing the processes that occur during these transitionalperiods. The proposed research will characterize the speci?c roles of thyroid hormone in post-embryonicdevelopmental progression; will identify genes and pathways required for the development of adult characters;and will examine developmental and regulatory pathways in the context of natural developmental truncation.
| Hur, Matthew; Gistelinck, Charlotte A; Huber, Philippe et al. (2018) MicroCT-Based Phenomics in the Zebrafish Skeleton Reveals Virtues of Deep Phenotyping in a Distributed Organ System. Zebrafish 15:77-78 |
| McMenamin, Sarah; Carter, Casey; Cooper, Wiliam James (2017) Thyroid Hormone Stimulates the Onset of Adult Feeding Kinematics in Zebrafish. Zebrafish 14:517-525 |
| Hur, Matthew; Gistelinck, Charlotte A; Huber, Philippe et al. (2017) MicroCT-based phenomics in the zebrafish skeleton reveals virtues of deep phenotyping in a distributed organ system. Elife 6: |
