Publication Date

2012-05-09

Availability

Embargoed

Embargo Period

2014-05-09

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biology (Arts and Sciences)

Date of Defense

2012-04-13

First Committee Member

Athula H. Wikramanayake

Second Committee Member

Akira Chiba

Third Committee Member

Zhongmin Lu

Fourth Committee Member

Julia Dallman

Fifth Committee Member

Mary Lou King

Abstract

Data from diverse species within the deuterostomes (mouse, frog, fish, amphioxus, hemichordate, ascidians, sea urchin, sea star) and protostomes (annelids, planarians, nemerteans, mollusks) suggest that Wnt/β-catenin signaling determines posterior identity and thus patterns anterior-posterior body plan formation in most bilaterians. Moreover, nuclear β-catenin marks the gastrulation site in many metazoans including the cnidarians. The activation of Wnt/β-catenin signaling at one pole of these embryos is highly influenced by the animal-vegetal (AV) axis of the oocyte. This primary egg axis is specified during oogenesis, however, the maternal mechanisms that establish AV egg polarity and subsequently mediate asymmetric activation of Wnt/β-catenin signaling are largely unknown. For my dissertation research I used the morphologically simple sea urchin embryo to elucidate the roles of critical evolutionarily conserved components that are pre-localized in the unfertilized egg, and are used to establish the primary body axis during early embryonic development. I studied two scaffolding proteins, Dishevelled (Dsh) and axis inhibition protein (Axin), which serve as key regulators of the Wnt/β-catenin pathway. Dsh and Axin each play crucial roles in patterning the early embryo along the AV axis by regulating endomesoderm specification. Work done on Dsh revealed a novel vegetal cortical domain (VCD) that is specified during oogenesis, maintained after fertilization, and inherited and partitioned by the most vegetal blastomeres to locally activate endomesoderm specification in the sea urchin embryo. Since the AV axis is found in nearly all metazoan eggs, this finding suggests that the VCD might be an evolutionarily conserved mechanism for the establishment of the AV axis in metazoan ova. Work done on Axin suggests that it plays an evolutionarily conserved role in the negative regulation of the Wnt/β-catenin pathway in sea urchin embryos, similar to the function that Axin plays in the vertebrates. Moreover, while Axin plays a crucial role in patterning the dorsal-ventral axis in vertebrates by maintaining ventral cell fates, my results suggest that Axin is required to prevent the Veg1 tier ectodermal progeny from becoming endoderm. This result suggests a novel mechanism for Axin in axis patterning in the sea urchin embryo. Furthermore, the data in sea urchins also raises the possibility that the ancestral role of Axin was to pattern the AV axis in basal deuterostomes before being co-opted to pattern the dorsal-ventral axis in vertebrates. In sum, the early patterning of the sea urchin embryos along the AV axis relies on locally concentrated Dsh at the VCD to specify endomesoderm at the vegetal pole, and on Axin to suppress endodermal cell fate in the more animal daughters of Veg1 tier progeny.

Keywords

Dishevelled; Axin; Animal-Vegetal axis; Vegetal cortical domain; Maternal determinants; Sea urchin

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