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SPECIFICATION OF MUSCLE CELL FATES

Award Number: R01AR045575
ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/05/1999
PERIOD OF PERFORMANCE END DATE: 04/30/2009

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SPECIFICATION OF MUSCLE CELL FATES - DESCRIPTION (provided by applicant): Skeletal muscles are comprised of two major cell types, slow and fast, that have distinct physiological, biochemical, morphological and developmental properties. The long-term goals of this work are to understand the mechanisms that regulate the formation and patterning of these different muscle types and how these mechanisms are altered in muscular diseases. Previous studies of zebrafish embryos have suggested that Hedgehog (Hh) produced by notochord and floor plate acts locally to specify slow muscle. Even though muscle precursor cells throughout the somite are apparently competent to respond to Hh, only a single monolayer precisely adjacent to the source of Hh, forms slow muscle. The proposed studies will use embryological and genetic methods to test a new hypothesis that accounts for this remarkably precise patterning: Two mechanisms limit the inductive action of Hh to immediately adjacent cells. First, notochord induces a subset of muscle precursors, in an Hh independent manner, to form adaxial cells, an epithelial monolayer that blankets the notochord. Then, in response to Hh signaling, cells in this monolayer express high levels of Patched and Hedgehog interacting protein that bind Hh at high affinity and limit its action. Thus, adaxial cells adjacent to the notochord receive high levels of Hh that induces them to become slow muscle, while at the same time, they reduce Hh signaling to more lateral cells that consequently form fast muscle.


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: 2008 ( Subtotal = $313,926 )
2008	2008	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	10	4/29/2008	NON-COMPETING CONTINUATION	$313,926
														Subtotal = $313,926

Issue Date FY: 2007 ( Subtotal = $320,332 )
2007	2007	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	9	4/26/2007	NON-COMPETING CONTINUATION	$320,332
														Subtotal = $320,332

Issue Date FY: 2006 ( Subtotal = $329,899 )
2006	2006	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	8	5/24/2006	NON-COMPETING CONTINUATION	$329,899
														Subtotal = $329,899

Issue Date FY: 2005 ( Subtotal = $338,027 )
2005	2005	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	7	5/16/2005	NON-COMPETING CONTINUATION	$338,027
														Subtotal = $338,027

Issue Date FY: 2004 ( Subtotal = $338,975 )
2004	2004	UNIVERSITY OF OREGON	5219 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	6	6/28/2004	COMPETING CONTINUATION	$338,975
														Subtotal = $338,975

Issue Date FY: 2003 ( Subtotal = $276,795 )
2003	2003	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	5		NON-COMPETING CONTINUATION	$276,795
														Subtotal = $276,795

Issue Date FY: 2002 ( Subtotal = $268,733 )
2002	2002	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	4	1/25/2002	NON-COMPETING CONTINUATION	$268,733
														Subtotal = $268,733

Issue Date FY: 2001 ( Subtotal = $260,906 )
2001	2001	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	3	2/8/2001	NON-COMPETING CONTINUATION	$260,906
														Subtotal = $260,906

Issue Date FY: 2000 ( Subtotal = $253,308 )
2000	2000	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	2	2/9/2000	NON-COMPETING CONTINUATION	$253,308
														Subtotal = $253,308

Issue Date FY: 1999 ( Subtotal = $262,489 )
1999	1999	UNIVERSITY OF OREGON	5215 UNIVERSITY OF OREGON	EUGENE	OR	97403	LANE	USA	Arthritis, Musculoskeletal and Skin Diseases Research	000	1	2/4/1999	NEW	$262,489
														Subtotal = $262,489

Grand Total All Awards = $2,963,390

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SPECIFICATION OF MUSCLE CELL FATES

Award Number: R01AR045575

ORGANIZATION: NATIONAL INSTITUTE OF ARTHRITIS & MUSCULOSKELETAL & SKIN DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/05/1999

PERIOD OF PERFORMANCE END DATE: 04/30/2009

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