Wednesday, October 1, 2025 10/1/2025

Molecular Interactions during Neural Crest Formation

Award Number: R01DE017914
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2007
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Molecular Interactions during Neural Crest Formation - Project Summary/Abstract. Neural crest cells (NC) are unique to vertebrates, arise early in development, emigrate from the dorsal aspect of the neural tube, and differentiate into a plethora of derivatives throughout the body, contributing neurons and glia of the peripheral nervous system, melanocytes, and craniofacial bone and cartilage amongst other derivatives. Failed NC development is associated with a large number of conditions known as Neurocristopathies, which include common orofacial clefts, aggressive cancers and rare syndromes. The long term goal of this research program is to advance our understanding of the earliest signaling events responsible for the formation of the NC. Currently signaling by WNT, FGF and BMP are amongst a few of key inputs recognized to be critical for the formation of NC, yet our understanding of the molecular mechanisms by which they execute their effects remain limited. To improve our knowledge of this events, it is critical to identify the effectors modulated by these pathways and to characterize their effects. The objectives of this proposal are: 1) to establish and characterize for the first time the role of TGFb /SMAD2-SMAD3 signaling during early facets of NC formation, prior to their allocation into the neural tube, migration or differentiation; and 2) to identify the effectors of the WNT and/or TGFb and characterize their role during early NC formation. Our Hypotheses are that the TGFb /SMAD2-SMAD3 signaling is required to launch the earliest events in NC formation, and that a combination of TGFb and WNT responsive molecules direct the specific acquisition of the NC lineage. To address these hypotheses our proposal is guided by 3 specific aims: 1) to demonstrate the requirement and contribution of the TGFb /SMAD2-SMAD3 signaling during early facets of NC formation, 2) to identify novel candidate effectors of WNT and/or TGFb and characterize their specific contributions to the acquisition of the NC fate, and 3) to assess their function in vivo in a vertebrate embryo. This innovative proposal takes advantage of a robust model of human NC formation based in pluripotent stem cells and classic chick embryology to, for the first time address the possible contribution of TGFb signaling (not BMPs) during this process and pursues an integrative approach addressing the combinatorial signaling of WNT and TGFb. The proposal is significant because the gains in this area will have impact in key aspects of fate acquisition and differentiation applicable to other cell types, and should improve our capacity to manage the many pathologies associated with NC.


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: 2025 ( Subtotal = $488,859 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	001	15	8/8/2025	NON-COMPETING CONTINUATION	$0
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	15	7/22/2025	NON-COMPETING CONTINUATION	$488,859
														Subtotal = $488,859

Issue Date FY: 2024 ( Subtotal = $479,083 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	14	7/9/2024	NON-COMPETING CONTINUATION	$479,083
														Subtotal = $479,083

Issue Date FY: 2023 ( Subtotal = $488,859 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFC BUILDING	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	13	7/18/2023	NON-COMPETING CONTINUATION	$488,859
														Subtotal = $488,859

Issue Date FY: 2022 ( Subtotal = $483,970 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	12	7/5/2022	NON-COMPETING CONTINUATION	$483,970
														Subtotal = $483,970

Issue Date FY: 2021 ( Subtotal = $488,662 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	002	11	7/28/2021	COMPETING CONTINUATION	$488,858
2021	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	10	4/2/2021	SUPPLEMENT FOR EXPANSION	$893
2021	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	900 UNIVERSITY AVE	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	001	10	4/14/2021	SUPPLEMENT FOR EXPANSION	-$1,089
														Subtotal = $488,662

Issue Date FY: 2020 ( Subtotal = -$893 )
2020	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	10	5/3/2020	SUPPLEMENT FOR EXPANSION	-$893
														Subtotal = -$893

Issue Date FY: 2017 ( Subtotal = $557,443 )
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	002	10	9/12/2017	SUPPLEMENT FOR EXPANSION	$105,771
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	10	7/5/2017	NON-COMPETING CONTINUATION	$387,604
2017	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA AT RIVERSIDE	200 UNIVERSTY OFFICE BLDG	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	001	10	9/6/2017	SUPPLEMENT FOR EXPANSION	$64,068
														Subtotal = $557,443

Issue Date FY: 2016 ( Subtotal = $387,500 )
2016	2016	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	000	9	7/29/2016	NON-COMPETING CONTINUATION	$387,500
														Subtotal = $387,500

Issue Date FY: 2015 ( Subtotal = $357,063 )
2015	2015	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	002	8	7/31/2015	NON-COMPETING CONTINUATION	$385,208
2015	2014	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	003	7	8/7/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$301,548
2015	2014	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	004	7	8/12/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$301,548
2015	2014	REGENTS, UNIVERSITY OF CALIFORNIA	POST OFFICE BOX 112	RIVERSIDE	CA	92521	RIVERSIDE	USA	Oral Diseases and Disorders Research	001	7	7/7/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$301,548
2015	2014	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Oral Diseases and Disorders Research	000	6	7/6/2015	COMPETING CONTINUATION	-$329,693
														Subtotal = $357,063

Issue Date FY: 2014 ( Subtotal = $404,114 )
2014	2014	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Oral Diseases and Disorders Research	000	6	6/5/2014	COMPETING CONTINUATION	$404,114
														Subtotal = $404,114

Issue Date FY: 2011 ( Subtotal = $392,531 )
2011	2011	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Oral Diseases and Disorders Research	000	5	7/11/2011	NON-COMPETING CONTINUATION	$392,531
														Subtotal = $392,531

Issue Date FY: 2010 ( Subtotal = $504,684 )
2010	2010	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Trans-NIH Recovery Act Research Support	000	3	3/8/2010	SUPPLEMENT FOR EXPANSION	$100,000
2010	2010	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Oral Diseases and Disorders Research	001	4	7/16/2010	NON-COMPETING CONTINUATION	$404,684
														Subtotal = $504,684

Issue Date FY: 2009 ( Subtotal = $398,369 )
2009	2009	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Oral Diseases and Disorders Research	000	3	7/17/2009	NON-COMPETING CONTINUATION	$398,369
														Subtotal = $398,369

Issue Date FY: 2008 ( Subtotal = $409,199 )
2008	2008	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Oral Diseases and Disorders Research	000	2	7/15/2008	NON-COMPETING CONTINUATION	$409,199
														Subtotal = $409,199

Issue Date FY: 2007 ( Subtotal = $412,605 )
2007	2007	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Oral Diseases and Disorders Research	000	1	7/17/2007	NEW	$412,605
														Subtotal = $412,605

Grand Total All Awards = $6,252,048

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Molecular Interactions during Neural Crest Formation

Award Number: R01DE017914

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2007

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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