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MOLECULAR ANALYSIS OF THE SEGEMENTATION CLOCK

Award Number: R01HD043158
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2003
PERIOD OF PERFORMANCE END DATE: 03/31/2012

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MOLECULAR ANALYSIS OF THE SEGEMENTATION CLOCK - DESCRIPTION (provided by applicant): 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2011 ( Subtotal = $219,658 )
2011	2011	INSTITUT/GENETIQUE/BIOLOGIE MOLEC/CELL	BP 10142	ILLKIRCH				FRA	Child Health and Human Development Extramural Research	000	10	4/15/2011	NON-COMPETING CONTINUATION	$199,689
2011	2011	INSTITUT/GENETIQUE/BIOLOGIE MOLEC/CELL	BP 10142	ILLKIRCH				FRA	Child Health and Human Development Extramural Research	001	10	6/10/2011	NON-COMPETING CONTINUATION	$19,969
														Subtotal = $219,658

Issue Date FY: 2010 ( Subtotal = $212,578 )
2010	2010	INSTITUT/GENETIQUE/BIOLOGIE MOLEC/CELL	BP 10142	ILLKIRCH				FRA	Child Health and Human Development Extramural Research	002	9	4/15/2010	NON-COMPETING CONTINUATION	$221,876
2010	2009	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 EAST 50TH STREET	KANSAS CITY	MO	64110	JACKSON	USA	Child Health and Human Development Extramural Research	001	7	1/26/2010	NON-COMPETING CONTINUATION	-$28,986
2010	2009	INSTITUT/GENETIQUE/BIOLOGIE MOLEC/CELL	BP 10142	ILLKIRCH				FRA	Child Health and Human Development Extramural Research	000	8	1/26/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$19,688
														Subtotal = $212,578

Issue Date FY: 2009 ( Subtotal = $329,949 )
2009	2009	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 EAST 50TH STREET	KANSAS CITY	MO	64110	JACKSON	USA	Child Health and Human Development Extramural Research	000	7	6/5/2009	NON-COMPETING CONTINUATION	$329,949
														Subtotal = $329,949

Issue Date FY: 2008 ( Subtotal = $329,949 )
2008	2008	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 EAST 50TH STREET	KANSAS CITY	MO	64110	JACKSON	USA	Child Health and Human Development Extramural Research	000	6	4/2/2008	NON-COMPETING CONTINUATION	$329,949
														Subtotal = $329,949

Issue Date FY: 2007 ( Subtotal = $336,683 )
2007	2007	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 EAST 50TH STREET	KANSAS CITY	MO	64110	JACKSON	USA	Child Health and Human Development Extramural Research	000	5	3/22/2007	COMPETING CONTINUATION	$336,683
														Subtotal = $336,683

Issue Date FY: 2006 ( Subtotal = $279,474 )
2006	2006	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 EAST 50TH STREET	KANSAS CITY	MO	64110	JACKSON	USA	Child Health and Human Development Extramural Research	000	4	3/2/2006	NON-COMPETING CONTINUATION	$279,474
														Subtotal = $279,474

Issue Date FY: 2005 ( Subtotal = $286,200 )
2005	2005	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 EAST 50TH STREET	KANSAS CITY	MO	64110	JACKSON	USA	Child Health and Human Development Extramural Research	000	3	2/4/2005	NON-COMPETING CONTINUATION	$286,200
														Subtotal = $286,200

Issue Date FY: 2004 ( Subtotal = $286,200 )
2004	2004	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 EAST 50TH STREET	KANSAS CITY	MO	64110	JACKSON	USA	Child Health and Human Development Extramural Research	000	2	2/4/2004	NON-COMPETING CONTINUATION	$286,200
														Subtotal = $286,200

Issue Date FY: 2003 ( Subtotal = $286,200 )
2003	2003	STOWERS INSTITUTE FOR MEDICAL RESEARCH	1000 EAST 50TH STREET	KANSAS CITY	MO	64110	JACKSON	USA	Child Health and Human Development Extramural Research	000	1		NEW	$286,200
														Subtotal = $286,200

Grand Total All Awards = $2,566,891

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MOLECULAR ANALYSIS OF THE SEGEMENTATION CLOCK

Award Number: R01HD043158

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2003

PERIOD OF PERFORMANCE END DATE: 03/31/2012

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