The vertebrate body is built on a metameric organization which consists of a repetition along the antero- posterior (AP) axis of functionally equivalent units, each comprising a vertebra, its associated muscles, peripheral nerves and blood vessels. These units are not, however, strictly equivalent along the axis and exhibit regionalization along the different anatomical domains. The goal of our research is to understand how this complex pattern is established during embryogenesis. Congenital vertebral malformations in humans represent a major therapeutic challenge due to the intricate neural and musculoskeletal anatomy of the spine. Understanding the genetic and developmental mechanisms which control somitic/vertebral patterning would be invaluable towards prevention of these birth defects. The segmented distribution of the vertebrae derives from the earlier metameric pattern of the embryonic somites whose production has been linked to a molecular oscillator, the segmentation clock. Under the influence of Hox genes, the derivatives of the embryonic somites become subsequently regionalized to contribute to the different anatomical domains along the body axis. In this grant, we propose to continue our studies on the segmental patterning and on the subsequent regionalization of the body axis in the chicken embryo. We will focus on three related issues.
In Aim 1, we will continue our characterization of the segmentation process and of the associated oscillator. Preliminary microarray studies in the mouse embryo have revealed a far greater complexity of the oscillator than we anticipated. This led us to reconsider our approach of the study of the segmentation clock mechanism. We propose to move to a more integrated level in Aim1 and to complete a microarray study of the chicken segmentation clock and of the paraxial mesoderm maturation in normal and in various experimental conditions. We will use these experiments to reconstruct genetic networks that could help identify key players in the clock mechanism.
In Aim 2, we will investigate the details of the production of the paraxial mesoderm from its progenitors in the primitive streak with a particular focus on the stem cells which generate part of this tissue. We will continue our studies of the role of Hox genes in paraxial mesoderm regionalization. Our recent results show that Hox genes control the ingression of precursors of paraxial mesoderm from the epiblast into the primitive streak.
In Aim 3, we will try to understand the molecular and cellular aspects of cell ingression which are controlled by Hox genes. From these studies, we expect to gain significant insights into our understanding of the segmentation clock mechanism and of Hox gene function in early stages of mesoderm patterning.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD043158-09
Application #
8018649
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Javois, Lorette Claire
Project Start
2003-03-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
9
Fiscal Year
2010
Total Cost
$221,876
Indirect Cost
Name
Institute/Genetique/Biologie Molec/Cell
Department
Type
DUNS #
771980620
City
Illkirch
State
Country
France
Zip Code
67404
Chal, Jérome; Guillot, Charlène; Pourquié, Olivier (2017) PAPC couples the segmentation clock to somite morphogenesis by regulating N-cadherin-dependent adhesion. Development 144:664-676
Denans, Nicolas; Iimura, Tadahiro; Pourquié, Olivier (2015) Hox genes control vertebrate body elongation by collinear Wnt repression. Elife 4:
Pourquie, Olivier (2011) Vertebrate segmentation: from cyclic gene networks to scoliosis. Cell 145:650-63
Krol, Aurelie J; Roellig, Daniela; Dequeant, Mary-Lee et al. (2011) Evolutionary plasticity of segmentation clock networks. Development 138:2783-92
Bénazéraf, Bertrand; Francois, Paul; Baker, Ruth E et al. (2010) A random cell motility gradient downstream of FGF controls elongation of an amniote embryo. Nature 466:248-52
Zhang, Shaobing O; Mathur, Sachin; Hattem, Gaye et al. (2010) Sex-dimorphic gene expression and ineffective dosage compensation of Z-linked genes in gastrulating chicken embryos. BMC Genomics 11:13
Wright, David; Ferjentsik, Zoltan; Chong, Shang-Wei et al. (2009) Cyclic Nrarp mRNA expression is regulated by the somitic oscillator but Nrarp protein levels do not oscillate. Dev Dyn 238:3043-3055
Iimura, Tadahiro; Denans, Nicolas; Pourquie, Olivier (2009) Establishment of Hox vertebral identities in the embryonic spine precursors. Curr Top Dev Biol 88:201-34
Gomez, Céline; Pourquié, Olivier (2009) Developmental control of segment numbers in vertebrates. J Exp Zool B Mol Dev Evol 312:533-44
Iimura, Tadahiro; Pourquie, Olivier (2008) Manipulation and electroporation of the avian segmental plate and somites in vitro. Methods Cell Biol 87:257-70

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