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Molecular mechanisms driving cessation of neural crest migration and aggregation into cranial ganglia

Award Number: F31DE031154
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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Molecular mechanisms driving cessation of neural crest migration and aggregation into cranial ganglia - Proposal Summary Neural crest cells are an important stem-like cell population characterized by their multipotency and migratory ability. Originating within the forming central nervous system, neural crest cells undergo a spatiotemporally regulated epithelial-to-mesenchymal transition (EMT) to leave the neural tube and become migratory. They then migrate extensively throughout the developing embryo, giving rise to a wide range of derivatives as diverse as elements of the craniofacial skeleton and peripheral nervous system. In the post- migratory phase, neural crest cells condense into different structures, a process that involves loss of migratory characteristics, perhaps reflecting the reverse of the EMT process. While neural crest EMT has been studied extensively, the mechanisms underlying the condensation of neural crest cells to form final derivatives is far less well characterized. To address this knowledge gap, we propose to identify transcriptional changes that occur during gangliogenesis with the goal of identifying those mediating alterations in intercellular adhesion required for neural crest condensation into peripheral ganglia. Our hypothesis is that the gene regulatory mechanisms that play a role during peripheral ganglion formation may reflect a reversal of the EMT process. The goal is to uncover the molecular mechanisms that drive condensation of neural crest cells into ganglia. These may in turn lead to clues regarding the underlying cause of certain types of neurocristopathies like familial dysautonomia and neural crest-derived cancers like neuroblastoma and pheochromocytoma. Aim 1: RNA-sequencing of pure populations of post-migratory cranial neural crest cells: RNA-sequencing of isolated condensing cranial neural crest cells will allow us to identify novel transcription factors and adhesion molecules that may drive neural crest condensation into cranial ganglia. Aim 2: Functional analysis of genes selectively upregulated upon condensation to form ganglia: Identified upregulated genes in condensing cranial neural crest cells will be validated by in situ hybridization and Hybridization Chain Reaction. We will then perform systematic loss-of-function and ectopic expression experiments on selected genes to examine their role in regulating condensation into and differentiation of peripheral ganglia. Aim 3: Characterization of cis-regulatory elements modulating gene expression during ganglion condensation: To identify putative enhancers driving gene expression during cranial neural crest condensation, we will perform ATAC-sequencing to identify conserved noncoding regions in the genome that are accessible to transcription factors during cranial neural crest condensation.


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 = $49,774 )
2025	2025	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	5	4/4/2025	NON-COMPETING CONTINUATION	$49,774
														Subtotal = $49,774

Issue Date FY: 2024 ( Subtotal = $49,774 )
2024	2024	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	4	6/26/2024	NON-COMPETING CONTINUATION	$49,774
														Subtotal = $49,774

Issue Date FY: 2023 ( Subtotal = $48,494 )
2023	2023	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	3	5/18/2023	NON-COMPETING CONTINUATION	$48,494
														Subtotal = $48,494

Issue Date FY: 2022 ( Subtotal = $47,552 )
2022	2022	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	7/19/2022	NON-COMPETING CONTINUATION	$47,552
														Subtotal = $47,552

Issue Date FY: 2021 ( Subtotal = $46,836 )
2021	2021	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Oral Diseases and Disorders Research	001	1	6/15/2021	NEW	$0
2021	2021	CALIFORNIA INSTITUTE OF TECHNOLOGY	1200 E CALIFORNIA BLVD	PASADENA	CA	91125	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	1	6/15/2021	NEW	$46,836
														Subtotal = $46,836

Grand Total All Awards = $242,430

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Molecular mechanisms driving cessation of neural crest migration and aggregation into cranial ganglia

Award Number: F31DE031154

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

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