The early axiation processes in embryos produce a provisional organization that must be converted into the definitive anatomy of the adult body plan. Intermediate organizing processes adapt the limited organization of the embryo to that body plan.. Though described well in Drosphila, these processes are still poorly understood in vertebrates. During gastrulation and neurulation, patterning occurs through extensive cell movements, transient patterns of gene expression, and intercellular signaling. We are concerned with four important features of these intermediate processes: 1) the coordination between morphogenesis and gene expression in the mesoderm during gastrulation, 2) the segmentation of the pre-somitic mesoderm to form segmented somites, 3) the response of the ectoderm to the first inductive signals to define the extent of the neural plate, and 4) the transformation of the anterior neural structures into posterior ones. Four genes that are intimately involved with these processes will be studied in depth. The Xombi gene has been shown to be part of a network of reactions important for mesoderm induction and to be specifically involved in gastrulation movements. We will try to understand the specific targets of Xombi and the signals that produce its dynamic pattern of RNA expression. The hairy gene is the only homolog of Drosophila pair rule gene that is expressed in a pattern related to segmental organization in vertebrates. Its expression transiently in the caudal domain of the presomitic mesoderm suggests that its regulation is connected to vertebrate segmentation. We propose to study the detail the transcriptional regulation of the hairy gene, using the recently developed tool of transgenesis in Xenopus. We have recently identified a novel gene called geminin, which is the first gene expressed in the presumptive neural plate. It responds to the primary neural inducers, such as chordin and noggin, and it acts to suppress BMP4 expression. We wish to understand the biochemical role of geminin and the regulatory factors that determine its spatial distribution. Finally , it has been a puzzle that the primary neural inducers generate anterior but no posterior neural structures. We have found that wnt8 may have a role in """"""""caudalizing"""""""" these early neural signals and we propose to investigate this process further. In all of these studies, we hope to develop a better understanding of how the early organization of the egg is converted into the characteristic features of vertebrate anatomy. In the process, we will be investigating signaling pathways that may be use in many contexts of human biology.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Henken, Deborah B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Simakov, Oleg; Kawashima, Takeshi; Marl├ętaz, Ferdinand et al. (2015) Hemichordate genomes and deuterostome origins. Nature 527:459-65
Freeman, Robert; Ikuta, Tetsuro; Wu, Michael et al. (2012) Identical genomic organization of two hemichordate hox clusters. Curr Biol 22:2053-8
Darras, Sebastien; Gerhart, John; Terasaki, Mark et al. (2011) *-catenin specifies the endomesoderm and defines the posterior organizer of the hemichordate Saccoglossus kowalevskii. Development 138:959-70
Springer, Michael; Weissman, Jonathan S; Kirschner, Marc W (2010) A general lack of compensation for gene dosage in yeast. Mol Syst Biol 6:368
DeLuna, Alexander; Springer, Michael; Kirschner, Marc W et al. (2010) Need-based up-regulation of protein levels in response to deletion of their duplicate genes. PLoS Biol 8:e1000347
Goentoro, Lea; Shoval, Oren; Kirschner, Marc W et al. (2009) The incoherent feedforward loop can provide fold-change detection in gene regulation. Mol Cell 36:894-9
Jorgensen, Paul; Steen, Judith A J; Steen, Hanno et al. (2009) The mechanism and pattern of yolk consumption provide insight into embryonic nutrition in Xenopus. Development 136:1539-48
Goentoro, Lea; Kirschner, Marc W (2009) Evidence that fold-change, and not absolute level, of beta-catenin dictates Wnt signaling. Mol Cell 36:872-84
Freeman Jr, R M; Wu, M; Cordonnier-Pratt, M-M et al. (2008) cDNA sequences for transcription factors and signaling proteins of the hemichordate Saccoglossus kowalevskii: efficacy of the expressed sequence tag (EST) approach for evolutionary and developmental studies of a new organism. Biol Bull 214:284-302
Ohtsuki, Hisashi; Bordalo, Pedro; Nowak, Martin A (2007) The one-third law of evolutionary dynamics. J Theor Biol 249:289-95

Showing the most recent 10 out of 18 publications