GERM LAYER SPECIFICATION
Principal Investigator: D R McClay
Abstract: In deuterostomes, endoderm and mesoderm initially are cospecified as endomesoderm, and later subdivided into definitive endoderm and mesoderm by cell-cell signaling. Ectoderm depends upon signals from the endomesoderm for its axial properties. In the first phase of this project we established beta-catenin as the earliest known molecule required for specification of endomesoderm in the sea urchin embryo, a prototype deuterostome. We established that a Delta-Notch signal is responsible for the subdivision of endomesoderm into endoderm and mesoderm, and we collaborated in the assembly of a large provisional Gene Regulatory Network (GRN) model for endomesoderm cell specification. This proposal has three overriding specific aims that extend our knowledge of the gene regulatory network concept. I. The micromere gene regulatory network: The aim is to better understand the activation of the micromere GRN including the release of three distinct inductive signals from micromeres during the first 7-9 cleavages. Our first specific aim is to establish (i) how components in the egg vegetal cortex activate the network; (ii) the identity and function of the early endoderm induction signal (iii) how wnt 8, an autocrine signal in micromeres, is activated and regulates downstream network function, and (iv) how micromere GRN transcription factors set up the signal to begin an epithelial-mesenchymal transition. II. The endomesoderm gene regulatory network: Preliminary data suggests there are three distinct Notch signals necessary for endomesoderm specification during the first 10 cleavages. The first signal is from micromere to macromere to separate mesoderm from endomesoderm. The second Notch signal appears to reinforce the nascent mesoderm-endoderm boundary and the third Notch signal appears to occur later in the endoderm. This aim asks how the sequential use of the Notch signaling pathway fits into the gene regulatory network spatially and temporally in three locations at three different times, all within the first 10 cleavages. Ill. The oral-aboral gene regulatory network: This aim focuses on how oral-aboral specification is induced by endomesoderm derivatives, through BMP and p38 MAP kinase, and how the oral aboral gene regulatory network is organized. Ultimately, the oral-aboral ectoderm provides positional cues to the skeletogenic mesenchyme in the blastocoel beneath this epithelium. This network eventually will enable us to explore how positional cues are produced and displayed for later morphogenetic patterning.
Funding Period: 1999-09-02 - 2008-03-31
more information: NIH RePORT
- A Fringe-modified Notch signal affects specification of mesoderm and endoderm in the sea urchin embryoRobert E Peterson
Department of Biology and Developmental, Cell, and Molecular Biology Group, Duke University, Box 91000, Durham, NC 27708, USA
Dev Biol 282:126-37. 2005..Taken together, the results show that Fringe is necessary both for maternal and zygotic Notch signals, and these Notch signals affect specification of mesoderm and endoderm...
- Hedgehog signaling patterns mesoderm in the sea urchinKatherine D Walton
Department of Biology, Duke University, Box 90338, Durham, NC 27708, USA
Dev Biol 331:26-37. 2009..Together the data support the requirement of Hh signaling in patterning each of the mesoderm subtypes in the sea urchin embryo...
- Chordin is required for neural but not axial development in sea urchin embryosCynthia A Bradham
Biology Department, Boston University, 24 Cummington, Boston, MA, USA
Dev Biol 328:221-33. 2009..Chd expression and synB-positive neural development are both downstream from p38 MAPK and Nodal, but not Goosecoid. These data are summarized in a model for synB neural development...
- Twist is an essential regulator of the skeletogenic gene regulatory network in the sea urchin embryoShu Yu Wu
Department of Biology, French Family Science Center, Duke University, Durham, NC 27708, USA
Dev Biol 319:406-15. 2008..These data illustrate the significance of regulatory state maintenance and continuous progression during cell specification, and the dynamics of the sequential events that depend on those earlier regulatory states...
- The Snail repressor is required for PMC ingression in the sea urchin embryoShu Yu Wu
DCMB Group, Biology Department, Duke University, Durham, NC 27708, USA
Development 134:1061-70. 2007....
- The genome of the sea urchin Strongylocentrotus purpuratusErica Sodergren
Science 314:941-52. 2006..This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes...
- Protein tyrosine and serine-threonine phosphatases in the sea urchin, Strongylocentrotus purpuratus: identification and potential functionsC A Byrum
Developmental, Cell, and Molecular Biology Group, Box 91000, Duke University, Durham, NC 27708, USA
Dev Biol 300:194-218. 2006..Finally, to assess roles of annotated phosphatases in endomesoderm formation, a literature review of phosphatase functions in model organisms was superimposed on sea urchin developmental pathways to predict areas of functional activity...
- A genome-wide survey of the evolutionarily conserved Wnt pathways in the sea urchin Strongylocentrotus purpuratusJenifer C Croce
Developmental, Molecular, and Cellular Biology Group, Duke University, DCMB Group, LSRC Bldg Rm B359A, Research Drive, Durham, NC 27708, USA
Dev Biol 300:121-31. 2006..Thus, these analyses produce new inputs in the evolutionary history of the Wnt genes in an animal occupying a position that offers great insights into the basal properties of deuterostomes...
- Genomics and expression profiles of the Hedgehog and Notch signaling pathways in sea urchin developmentKatherine D Walton
Developmental, Cellular, and Molecular Biology Group, Duke University, Durham, NC 27710, USA
Dev Biol 300:153-64. 2006..Functional analyses in future studies will embed these pathways into the growing knowledge of gene regulatory networks that govern early specification and morphogenesis...
- Repression of mesodermal fate by foxa, a key endoderm regulator of the sea urchin embryoPaola Oliveri
Division of Biology, 156 29, California Institute of Technology, Pasadena, CA 91125, USA
Development 133:4173-81. 2006..These experiments show that the foxa gene is a component of three distinct embryonic gene regulatory networks...
- Lineage-specific expansions provide genomic complexity among sea urchin GTPasesWendy S Beane
Department of Biology, Developmental, Cell and Molecular Group, Duke University, Box 91000, Durham, NC 27708, USA
Dev Biol 300:165-79. 2006..These findings suggest that lineage-specific expansions may be an important component of genomic evolution in signal transduction...
- The genomic underpinnings of apoptosis in Strongylocentrotus purpuratusAnthony J Robertson
Mount Desert Island Biological Laboratory, Salisbury Cove, ME 04672, USA
Dev Biol 300:321-34. 2006....
- RhoA regulates initiation of invagination, but not convergent extension, during sea urchin gastrulationWendy S Beane
Department of Biology, Developmental, Cell and Molecular Group, Duke University, PO Box 91000, Durham, NC 27708, USA
Dev Biol 292:213-25. 2006..Instead, the results support the hypothesis that RhoA serves as a trigger to initiate invagination, and once initiation occurs, RhoA activity is no longer involved in subsequent gastrulation movements...
- Frizzled5/8 is required in secondary mesenchyme cells to initiate archenteron invagination during sea urchin developmentJenifer Croce
Unite de Biologie du Developpement, UMR 7009, CNRS, Universite Pierre et Marie Curie, Observatoire Oceanologique, Villefranche sur Mer, France
Development 133:547-57. 2006..Taken together, the results suggest that Fz5/8 plays a crucial role specifically in SMCs to control primary invagination during sea urchin gastrulation...
- Blocking Dishevelled signaling in the noncanonical Wnt pathway in sea urchins disrupts endoderm formation and spiculogenesis, but not secondary mesoderm formationChristine A Byrum
Department of Zoology, University of Hawaii at Manoa, Honolulu, Hawaii, USA
Dev Dyn 238:1649-65. 2009....