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Mechanisms of neural patterning and the generation of neural diversity in the brain

Award Number: R01EY017916
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2007
PERIOD OF PERFORMANCE END DATE: 05/31/2029

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Mechanisms of neural patterning and the generation of neural diversity in the brain - Mechanisms of neural patterning and the generation of neural diversity in the brain. We have shown that neural diversity in the optic lobe of Drosophila is generated by three mechanisms: Each neural stem cell (neuroblast; NB) expresses sequentially a series of temporal transcription factors (tTF) and divides to produce an intermediate precursor that divides once more to generate a NotchON and a NotchOFF neuron. The neuroepithelium that generates NBs is patterned by spatial TFs (sTFs) and by signaling molecules. Different regions of the neuroepithelium generate NBs that undergo the same tTF series but produce different neurons due to spatial patterning of the neuroepithelium of origin. We offer to continue our investigations into the development of the medulla and address whether stochastic factors complement the deterministic and intrinsic programs that generate diversity (Aim 1) and investigate how many different spatial regions comprise the NE and how this spatial patterning controls the stoichiometry of neurons (Aim 2). There are many more than 800 NBs to produce neurons populating the 800 medulla columns that process visual information from the 800 unit-eyes in the fly retina. We will test whether an excess number of the same neurons is produced from all the NBs and culled later by apoptosis, or whether the temporal series progresses independently of cell cycle: In the latter case, the lack of coordination between the progression of the temporal series and cell cycle introduces a stochastic component that would allow flexibility in the identity (and number) of the neurons produced by each NB. The role of stochastic patterning of neural stem cells has been demonstrated in mammals but is very poorly understood. The repetitive structure and precise genetic manipulations in the fly optic lobe make this system ideal to address these questions: Aim 1: Progression of the temporal series and cell cycle: The many NBs (at least twice as many as columns) suggest that neurons are produced in excess and culled, or that each NB only produces stochastically a subset of the neurons. Aim 1.1: Do NBs produce excess numbers of neurons and those that do not find a partner are later culled by cell death? Aim 1.2: Is the progression of temporal windows coordinated with cell cycle? Aim 1.3: Are all temporal windows used to generate all the neurons that a given NB could produce? Aim 1.4: What is the temporal window of origin of the ~100 medulla neurons? Aim 1.5: Does the length of temporal windows determine the number of neurons produced at each temporal window? Aim 1.6: Does the speed of transition of temporal windows rely on regulation of RNA stability and/or translation status? Aim 2: Spatial patterning and epigenetic memory: How do NBs from different spatial domains undergo the same temporal series but produce different neurons in different stoichiometry? Aim 2.1: How does Dpp signaling generate at least three subdomains within one of the spatial domains? Aim 2.2: Define new spatial sub-domains using scRNAseq of neuroepithelial cells Aim 2.3: Is the spatial identity of neuroepithelial cells transmitted to NBs and neurons by epigenetic memory? Aim 2.4: Use scRNAseq to identify the neurons produced by each spatial domain. Aim 2.5: How does the integration of spatio-temporal patterning and Notch signaling control neuronal features?


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 = $546,358 )
2025	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	002	19	7/14/2025	NON-COMPETING CONTINUATION	$546,358
2025	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	001	18	2/24/2025	COMPETING CONTINUATION	$1
2025	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	17	2/24/2025	NON-COMPETING CONTINUATION	-$1
														Subtotal = $546,358

Issue Date FY: 2024 ( Subtotal = $548,194 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	18	6/17/2024	COMPETING CONTINUATION	$548,194
														Subtotal = $548,194

Issue Date FY: 2023 ( Subtotal = $396,250 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	17	6/7/2023	NON-COMPETING CONTINUATION	$396,250
														Subtotal = $396,250

Issue Date FY: 2022 ( Subtotal = $384,363 )
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	16	6/10/2022	NON-COMPETING CONTINUATION	$384,363
														Subtotal = $384,363

Issue Date FY: 2021 ( Subtotal = $384,362 )
2021	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	002	15	5/20/2021	NON-COMPETING CONTINUATION	$384,362
2021	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	001	14	10/21/2020	COMPETING CONTINUATION	$240
2021	2019	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	13	10/21/2020	NON-COMPETING CONTINUATION	-$240
														Subtotal = $384,362

Issue Date FY: 2020 ( Subtotal = $396,250 )
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	001	14	8/3/2020	COMPETING CONTINUATION	$396,250
2020	2019	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	13	6/8/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $396,250

Issue Date FY: 2019 ( Subtotal = $396,250 )
2019	2019	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	13	1/30/2019	NON-COMPETING CONTINUATION	$396,250
														Subtotal = $396,250

Issue Date FY: 2018 ( Subtotal = $396,250 )
2018	2018	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	001	12	5/7/2018	NON-COMPETING CONTINUATION	$39,625
2018	2018	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	12	2/5/2018	NON-COMPETING CONTINUATION	$356,625
														Subtotal = $396,250

Issue Date FY: 2017 ( Subtotal = $396,250 )
2017	2017	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	000	11	2/13/2017	NON-COMPETING CONTINUATION	$356,625
2017	2017	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Vision Research	001	11	7/17/2017	NON-COMPETING CONTINUATION	$39,625
														Subtotal = $396,250

Issue Date FY: 2016 ( Subtotal = $396,250 )
2016	2016	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	10	1/11/2016	COMPETING CONTINUATION	$396,250
														Subtotal = $396,250

Issue Date FY: 2015 ( Subtotal = $338,133 )
2015	2015	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	9	1/26/2015	NON-COMPETING CONTINUATION	$338,133
														Subtotal = $338,133

Issue Date FY: 2014 ( Subtotal = $338,134 )
2014	2014	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	8	2/26/2014	NON-COMPETING CONTINUATION	$338,134
														Subtotal = $338,134

Issue Date FY: 2013 ( Subtotal = $325,759 )
2013	2013	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	001	7	6/12/2013	NON-COMPETING CONTINUATION	$17,145
2013	2013	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	7	2/26/2013	NON-COMPETING CONTINUATION	$308,614
														Subtotal = $325,759

Issue Date FY: 2012 ( Subtotal = $342,904 )
2012	2012	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	6	1/10/2012	COMPETING CONTINUATION	$342,904
														Subtotal = $342,904

Issue Date FY: 2011 ( Subtotal = $323,655 )
2011	2011	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	5	1/14/2011	NON-COMPETING CONTINUATION	$303,427
2011	2011	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	001	5	5/18/2011	NON-COMPETING CONTINUATION	$20,228
														Subtotal = $323,655

Issue Date FY: 2010 ( Subtotal = $554,641 )
2010	2010	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	4	1/14/2010	NON-COMPETING CONTINUATION	$337,141
2010	2010	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Trans-NIH Recovery Act Research Support	001	4	9/30/2010	SUPPLEMENT FOR EXPANSION	$217,500
														Subtotal = $554,641

Issue Date FY: 2009 ( Subtotal = $340,668 )
2009	2009	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	001	3	4/20/2009	NON-COMPETING CONTINUATION	$34,067
2009	2009	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	3	1/26/2009	NON-COMPETING CONTINUATION	$306,601
														Subtotal = $340,668

Issue Date FY: 2008 ( Subtotal = $333,479 )
2008	2008	NEW YORK UNIVERSITY	SPONSORED PGMS ACCOUNTING	NEW YORK	NY	10003	NEW YORK	USA	Vision Research	000	2	3/6/2008	NON-COMPETING CONTINUATION	$333,479
														Subtotal = $333,479

Issue Date FY: 2007 ( Subtotal = $338,884 )
2007	2007	NEW YORK UNIVERSITY	726 BROADWAY, 2ND FL ROOM 271	NEW YORK-NEW YORK	NY	10003		USA	Vision Research	000	1	1/26/2007	NEW	$338,884
														Subtotal = $338,884

Grand Total All Awards = $7,477,034

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Mechanisms of neural patterning and the generation of neural diversity in the brain

Award Number: R01EY017916

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2007

PERIOD OF PERFORMANCE END DATE: 05/31/2029

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