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Regulation of neurodevelopmental cell behaviors in Ciona

Award Number: R01HD104825
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: 09/12/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Regulation of neurodevelopmental cell behaviors in Ciona - PROJECT SUMMARY/ABSTRACT The regulation of transient cell behaviors and regulatory “states” is indispensable for the development of multicellular organisms. Knowledge of the genetic architecture and emergent properties of these processes is also key to developing therapies for congenital diseases and neurodevelopmental syndromes based on cellular reprogramming or genome editing. The objective of this proposal is to characterize the regulation and functions of potentially important genes that control polarized neuronal migration and axon outgrowth in the Ciona larval nervous system, which shares many anatomical and molecular features with the larger systems of their close relatives the vertebrates. The central hypothesis is that these processes are controlled by precise developmental regulation of genes encoding rate-limiting components of diverse biochemical pathways, which may vary according to developmental stage and neuronal subtype. The rationale underlying the proposed research is that, by exploiting the genomic and cellular simplicity afforded by invariantly developing Ciona embryos, one can study these processes in vivo, with greater spatial and temporal resolution. With only 231 neurons and a fully mapped “connectome”, the Ciona nervous system offers a singular opportunity to understand cell behaviors and developmental trajectories in a chordate nervous system at single-cell resolution. The central hypothesis will be tested by pursuing three specific aims: 1) Testing the role of instrinsic and extrinsic TGFβ pathway components in dynamically but invariantly polarizing neuronal progenitors; 2) Investigating the causal links between regulation of effectors of receptor trafficking and precisely timed inversion of intracellular polarity and axon outgrowth orientation. 3) Investigating the role of collective epithelial sheet-like migration in precise positioning and morphogenesis of differentiated neurons, and testing the involvement of tight junction proteins in regulating this unusual mode of collective migration. These aims will be pursued using an innovative approach that combines cell lineage-specific, CRISPR/Cas9-based somatic gene knockouts and live fluorescence microscopy. The expected outcomes of the proposed work include identifying previously unrecognized functions for conserved but poorly studied genes in neurodevelopment, and understanding how precise control over neuronal subtype-specific polarized cell behaviors can be achieved through transcriptional regulation of both intrinsic and extrinsic effector genes.


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 = $311,572 )
2025	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Child Health and Human Development Extramural Research	000	4	6/17/2025	NON-COMPETING CONTINUATION	$311,572
														Subtotal = $311,572

Issue Date FY: 2024 ( Subtotal = $308,697 )
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Child Health and Human Development Extramural Research	000	3	6/6/2024	NON-COMPETING CONTINUATION	$308,697
														Subtotal = $308,697

Issue Date FY: 2023 ( Subtotal = $313,590 )
2023	2023	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Child Health and Human Development Extramural Research	000	2	6/14/2023	NON-COMPETING CONTINUATION	$313,590
														Subtotal = $313,590

Issue Date FY: 2022 ( Subtotal = $337,738 )
2022	2022	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Child Health and Human Development Extramural Research	000	1	9/9/2022	NEW	$337,738
														Subtotal = $337,738

Grand Total All Awards = $1,271,597

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Regulation of neurodevelopmental cell behaviors in Ciona

Award Number: R01HD104825

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: 09/12/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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