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Cell-cell communications in neural circuit assembly

Award Number: R01NS050835
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2005
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Cell-cell communications in neural circuit assembly - PROJECT SUMMARY A key question in neurobiology is how individual neurons precisely connect with each other to form functional circuits during development. Understanding the mechanisms of neural circuit assembly in the mammalian brain may provide insights into the etiology of human brain disorders. In the mammalian brain, each neuron on average forms connection with thousands of other neurons. The assembly of these complex circuits depends on cell-cell communication during many steps of neural development. In the previous three cycles of this grant, we have developed methods such as MADM (Mosaic Analysis with Double Markers) and viral-genetic manipulations in mice that allowed us to label and genetically manipulate specific neuron cell types, down to individual neurons, and study genes that play key roles in dendrite morphogenesis and target selection of axons. Specifically, we have recently identified two cell-surface proteins, Teneurin-3 (Ten3) and Latrophilin-2 (Lphn2), that are expressed in complementary patterns in the interconnected nodes of hippocampal network, following a “Ten3→Ten3, Lphn2→Lphn2” connectivity rule . We have shown that Lphn2 acts as a heterophilic repulsive ligand and Ten3 acts as a homophilic attractive ligand to direct Ten3+ proximal CA1 axons to selectively target to distal subiculum; at the same time, Ten3 acts as a repulsive ligand to direct Lphn2+ axons to proximal subiculum. We have also developed a method that allows us to profile cell-surface proteomes with exquisite sensitivity and spatiotemporal control. In this proposal, we will expand on both of these recent advances. Specifically, we will investigate whether Ten3 and Lphn2 instruct wiring specificity in multiple nodes of the extended hippocampal network and in other brain regions, how Ten3-Lphn2 interaction leads to axon repulsion, and whether G protein signaling is essential for Lphn2’s action as a receptor or a ligand. Complementary to the in-depth studies of Ten3 and Lphn2, we will use our cell-surface proteomic profiling methods to broadly survey changes of cell- surface proteomes from developing to mature neurons, and to identify new cell-surface proteins that regulate dendrite morphogenesis and neural circuit assembly.


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: 2026 ( Subtotal = $446,269 )
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	12/30/2025	NON-COMPETING CONTINUATION	$401,642
2026	2026	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	19	4/8/2026	NON-COMPETING CONTINUATION	$44,627
														Subtotal = $446,269

Issue Date FY: 2025 ( Subtotal = $446,178 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	18	7/23/2025	NON-COMPETING CONTINUATION	$44,617
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	12/31/2024	NON-COMPETING CONTINUATION	$401,561
														Subtotal = $446,178

Issue Date FY: 2024 ( Subtotal = $434,334 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	1/9/2024	NON-COMPETING CONTINUATION	$402,990
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	17	4/11/2024	NON-COMPETING CONTINUATION	$31,344
														Subtotal = $434,334

Issue Date FY: 2023 ( Subtotal = $445,996 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	16	1/31/2023	NON-COMPETING CONTINUATION	$44,600
2023	2023	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	1/11/2023	NON-COMPETING CONTINUATION	$401,396
														Subtotal = $445,996

Issue Date FY: 2022 ( Subtotal = $444,270 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	15	12/31/2021	COMPETING CONTINUATION	$444,270
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	15	8/24/2022	COMPETING CONTINUATION	$35,790
2022	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	12/23/2021	NON-COMPETING CONTINUATION	$0
2022	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	14	8/24/2022	NON-COMPETING CONTINUATION	-$35,790
														Subtotal = $444,270

Issue Date FY: 2020 ( Subtotal = $375,758 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	3/27/2020	NON-COMPETING CONTINUATION	$375,758
														Subtotal = $375,758

Issue Date FY: 2019 ( Subtotal = $374,585 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	4/9/2019	NON-COMPETING CONTINUATION	$374,585
														Subtotal = $374,585

Issue Date FY: 2018 ( Subtotal = $373,099 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	5/10/2018	NON-COMPETING CONTINUATION	$373,099
														Subtotal = $373,099

Issue Date FY: 2017 ( Subtotal = $371,399 )
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	3/10/2017	NON-COMPETING CONTINUATION	$334,258
2017	2017	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	5/26/2017	NON-COMPETING CONTINUATION	$37,141
														Subtotal = $371,399

Issue Date FY: 2016 ( Subtotal = $369,766 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	6/21/2016	COMPETING CONTINUATION	$369,766
														Subtotal = $369,766

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2013	STANFORD UNIVERSITY	616 SERRA STREET	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	11/21/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $353,888 )
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	5/16/2013	NON-COMPETING CONTINUATION	$23,838
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	12/19/2012	NON-COMPETING CONTINUATION	$330,050
														Subtotal = $353,888

Issue Date FY: 2012 ( Subtotal = $364,909 )
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	12/16/2011	NON-COMPETING CONTINUATION	$328,419
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	1/30/2012	NON-COMPETING CONTINUATION	$36,490
														Subtotal = $364,909

Issue Date FY: 2011 ( Subtotal = $363,173 )
2011	2011	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	12/9/2010	NON-COMPETING CONTINUATION	$333,526
2011	2011	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	6/6/2011	NON-COMPETING CONTINUATION	$29,647
														Subtotal = $363,173

Issue Date FY: 2010 ( Subtotal = $365,200 )
2010	2010	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/14/2009	NON-COMPETING CONTINUATION	$331,999
2010	2010	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	1/20/2010	NON-COMPETING CONTINUATION	$33,201
														Subtotal = $365,200

Issue Date FY: 2009 ( Subtotal = $366,058 )
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	2/27/2009	COMPETING CONTINUATION	$805
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/10/2009	COMPETING CONTINUATION	$365,253
														Subtotal = $366,058

Issue Date FY: 2008 ( Subtotal = $354,468 )
2008	2008	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/18/2007	NON-COMPETING CONTINUATION	$354,468
														Subtotal = $354,468

Issue Date FY: 2007 ( Subtotal = $355,062 )
2007	2007	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/19/2007	NON-COMPETING CONTINUATION	$355,062
														Subtotal = $355,062

Issue Date FY: 2006 ( Subtotal = $364,090 ) (Continued on the next page)
Grand Total All Awards = $7,334,189

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Cell-cell communications in neural circuit assembly

Award Number: R01NS050835

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/01/2005

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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