Evolution of vertebrates has been intimately linked to the advent of the neural crest, a migratory and multipotent cell population that gives rise to many defining characters of vertebrates, including a well-defined head and peripheral ganglia. These multipotent progenitor cells form at the border of neural and non-neural ectoderm in vertebrate embryos. The regulatory interactions predicted to underlie neural crest formation involve inductive signals (e.g. Wnt, BMP, FGF) that establish the neural plate border, by up-regulation of border specifier genes like Msx1/2, Pax3/7, and Zic. These border genes in turn regulate neural crest specifier genes like Slug/Snail, FoxDS and the SoxE family. Finally, neural crest specifiers turn on specific downstream targets that render the neural crest migratory and multipotent. The goal of the proposed study is to address whether the neural crest gene regulatory network of traditional vertebrate models is conserved to the base of vertebrates. Data from non-vertebrate chordates suggest this network is a vertebrate novelty and that neural crest evolution involved cooption of several transcriptional regulators to the neural plate border of the vertebrate ancestor. We will compare the neural crest gene regulatory network of traditional vertebrate models with that of sea lamprey, jawless fish that represent the most primitive extant vertebrates. Our preliminary results suggest that many neural crest derivatives, early migratory routes and some components of the neural crest gene network are conserved in lamprey. We will test for conservation at the level of deployment of these molecules at the neural plate border as well as ability to carry out similar functions. To explore events that led to the evolution of this important cell type and thus to the origin of vertebrate features, this proposal will address the following specific aims: 1) Examine whether key genes that function as neural plate border and neural crest specifiers are conserved in sequence and distribution between jawless and jawed vertebrates. 2) Establish connections within the network by morpholino-mediated knock-down of selected transcription factors;establish epistasis by examining the consequences on expression of other genes in the network and their ability to rescue the loss-of-function phenotype. 3) Isolate regulatory regions of amphioxus and lamprey """"""""specifier genes.""""""""

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE017911-05
Application #
8113902
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Scholnick, Steven
Project Start
2007-08-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$373,105
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
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Modrell, Melinda S; Hockman, Dorit; Uy, Benjamin et al. (2014) A fate-map for cranial sensory ganglia in the sea lamprey. Dev Biol 385:405-16
Green, Stephen A; Bronner, Marianne E (2014) The lamprey: a jawless vertebrate model system for examining origin of the neural crest and other vertebrate traits. Differentiation 87:44-51
Parker, Hugo J; Bronner, Marianne E; Krumlauf, Robb (2014) A Hox regulatory network of hindbrain segmentation is conserved to the base of vertebrates. Nature 514:490-3
Parker, Hugo J; Sauka-Spengler, Tatjana; Bronner, Marianne et al. (2014) A reporter assay in lamprey embryos reveals both functional conservation and elaboration of vertebrate enhancers. PLoS One 9:e85492
Smith, Jeramiah J; Kuraku, Shigehiro; Holt, Carson et al. (2013) Sequencing of the sea lamprey (Petromyzon marinus) genome provides insights into vertebrate evolution. Nat Genet 45:415-21, 421e1-2
Green, Stephen A; Bronner, Marianne E (2013) Gene duplications and the early evolution of neural crest development. Semin Cell Dev Biol 24:95-100
Uy, Benjamin R; Simoes-Costa, Marcos; Sauka-Spengler, Tatjana et al. (2012) Expression of Sox family genes in early lamprey development. Int J Dev Biol 56:377-83
Jayasena, Chathurani S; Bronner, Marianne E (2012) Rbms3 functions in craniofacial development by posttranscriptionally modulating TGF-β signaling. J Cell Biol 199:453-66
Bronner, Marianne E; LeDouarin, Nicole M (2012) Development and evolution of the neural crest: an overview. Dev Biol 366:2-9

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