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Signaling mechanisms underlying neural crest cell fate decisions

Award Number: F32DE029662
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Signaling mechanisms underlying neural crest cell fate decisions - The neural crest contributes a wide variety of cell types to the human face, giving rise to teeth, melanocytes, the craniofacial skeleton, and the peripheral nervous system. The diversification strategies used by the neural crest are still elusive, but seem to be highly sensitive to genetic perturbations because heritable diseases frequently disrupt neural crest development, which can impact craniofacial growth. Thus, clarifying how cell interactions bias neural crest cell fates could reveal mechanisms of disease progression, many of which remain obscure. To perform a systematic characterization of neural crest lineages and their developmental regulation by cell signaling, we have built upon our recent breakthroughs in single-cell transcriptomic analysis to include viral gene delivery for functional interrogation. Using barcode-based clonal lineage tracing and high- throughput genetic perturbations in vivo via ultrasound-guided injections of lentivirus into the forming cranial neural crest region, we will map how cell lineages interact and diversify to build the face. Based on our preliminary data, we hypothesize that neural crest cells utilize collective multipotency, and communicate via signaling interactions in the dorsal neural tube that balances molecular biasing of early neural crest cells towards fates in correct proportions. We will test this hypothesis by functional experiments targeting receptors and ligands in neural crest subpopulations, with special emphasis on genes that when mutated, can result in pathology. By assembling a global collaboration of experts in advanced imaging techniques, single-cell transcriptomics, and mammalian genetics, we will determine the disease mechanisms underlying failures in facial development, and in doing so, contribute valuable datasets for the craniofacial and neural crest biology communities. Successful completion of our research plan will illuminate potential avenues to manipulate the behavior of stem cells at the population-wide scale, and reveal how cell fate choices could be manipulated in specific locations in vivo to generate skeletal shape and form. This three- year postdoctoral training plan is an excellent opportunity for the candidate to train at a world-renowned medical research environment, while gaining a unique combination of skills, background and network that will make a clear path towards scientific independence.


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 = $0 )
2025	2023	REDACTED DUE TO PII		SOLNA				SWE	Oral Diseases and Disorders Research	001	3	4/24/2025	NON-COMPETING CONTINUATION	$0
2025	2023	KAROLINSKA INSTITUTET	NOBELS VAG 6	SOLNA				SWE	Oral Diseases and Disorders Research	000	3	4/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $76,852 )
2023	2023	REDACTED DUE TO PII		SOLNA				SWE	Oral Diseases and Disorders Research	003	3	9/7/2023	NON-COMPETING CONTINUATION	-$64,652
2023	2023	KAROLINSKA INSTITUTET	NOBELS VAG 6	SOLNA				SWE	Oral Diseases and Disorders Research	007	3	9/11/2023	NON-COMPETING CONTINUATION	$12,200
2023	2023	REDACTED DUE TO PII		SOLNA				SWE	Oral Diseases and Disorders Research	006	3	9/11/2023	NON-COMPETING CONTINUATION	$64,652
2023	2023	KAROLINSKA INSTITUTET	NOBELS VAG 6	SOLNA				SWE	Oral Diseases and Disorders Research	001	3	8/25/2023	NON-COMPETING CONTINUATION	$12,200
2023	2023	REDACTED DUE TO PII		SOLNA				SWE	Oral Diseases and Disorders Research	000	3	8/24/2023	NON-COMPETING CONTINUATION	$64,652
2023	2023	KAROLINSKA INSTITUTET	NOBELS VAG 6	SOLNA				SWE	Oral Diseases and Disorders Research	004	3	9/7/2023	NON-COMPETING CONTINUATION	-$12,200
2023	2022	KAROLINSKA INSTITUTET	NOBELS VAG 6	SOLNA				SWE	Oral Diseases and Disorders Research	005	2	9/11/2023	NON-COMPETING CONTINUATION	$11,950
2023	2022	KAROLINSKA INSTITUTET	NOBELS VAG 6	SOLNA				SWE	Oral Diseases and Disorders Research	002	2	9/7/2023	NON-COMPETING CONTINUATION	-$11,950
														Subtotal = $76,852

Issue Date FY: 2022 ( Subtotal = $72,534 )
2022	2022	KAROLINSKA INST	NOBELS VAG 6	SOLNA				SWE	Oral Diseases and Disorders Research	001	2	8/8/2022	NON-COMPETING CONTINUATION	$11,950
2022	2022	REDACTED DUE TO PII		SOLNA				SWE	Oral Diseases and Disorders Research	000	2	7/6/2022	NON-COMPETING CONTINUATION	$60,584
														Subtotal = $72,534

Issue Date FY: 2021 ( Subtotal = $69,362 )
2021	2021	REDACTED DUE TO PII		SOLNA	STOCKHOLM			SWE	Oral Diseases and Disorders Research	003	1	6/30/2021	NEW	$0
2021	2021	REDACTED DUE TO PII		SOLNA	STOCKHOLM			SWE	Oral Diseases and Disorders Research	000	1	5/24/2021	NEW	$57,512
2021	2021	REDACTED DUE TO PII		SOLNA	STOCKHOLM			SWE	Oral Diseases and Disorders Research	002	1	6/3/2021	NEW	$0
2021	2021	REDACTED DUE TO PII		SOLNA	STOCKHOLM			SWE	Oral Diseases and Disorders Research	001	1	6/3/2021	NEW	$11,850
														Subtotal = $69,362

Grand Total All Awards = $218,748

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Signaling mechanisms underlying neural crest cell fate decisions

Award Number: F32DE029662

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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