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Regulation of symmetric and asymmetric cell division during brain development

Award Number: R01NS096130
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: 03/15/2016
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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Regulation of symmetric and asymmetric cell division during brain development - DESCRIPTION (provided by applicant): Neural progenitor cells maintain a tight control of the balance between self-renewal and differentiation in the developing and adult brains and can respond to environmental cues to either switch on more proliferation or produce more differentiated cells. Such a homeostatic control is not only important for normal development but also critical for proper functioning of the brain. The long-term goal of our study is to understand how self- renewal and differentiation are regulated during brain development and to apply the obtained knowledge for developing better diagnostic tools and novel therapeutic approaches for treating developmental brain disorders and brain cancers. This application proposes to investigate a novel protein interaction network that is crucial for controlling symmetric (self-renewal) versus asymmetric (differentiation) cell division in neural progenitor cells. In our previous studies, we have demonstrated, using combined cellular, embryological, and genetic approaches, that the regulator of G protein signaling (RGS)-mediated ephrin-B reverse signaling pathway is essential for maintaining the neural progenitor cell state in the embryonic cerebral cortex and that the Ga subunit signaling pathway is important for activating neuronal differentiation. We have identified a mitotic kinesin that can interact with and recruit the ephrin B/RGS proteins into the midbody of dividing neural progenitor cells, suggesting that the role of the ephrin-B/RGS pathway in neural progenitor cell regulation is linked to cytokinesis, the final stage of cell division. In addition, we have recently identified several interacting proteins of th active Ga subunits and found that these proteins, similar to Gα subunit, could activate neurogenesis. We thus propose to further characterize the biochemical interaction of the ephrin-B/RGS/mitotic kinesin and Ga subunit interaction network and examine the potential function of these networks in shaping neural progenitor cells' decision to either divide symmetrically or asymmetrically. We anticipate that the data obtained from this study will ultimately help understand what and how molecular interactions in neural progenitor cells guides the balance between self-renewal and differentiation and how dysregulation in these networks may lead to certain developmental brain disorders or tumorigenesis.


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: 2022 ( Subtotal = $0 )
2022	2020	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	8/9/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $371,875 )
2020	2020	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	7/28/2020	NON-COMPETING CONTINUATION	$0
2020	2020	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	2/24/2020	NON-COMPETING CONTINUATION	$371,875
														Subtotal = $371,875

Issue Date FY: 2019 ( Subtotal = $371,875 )
2019	2019	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/6/2019	NON-COMPETING CONTINUATION	$371,875
														Subtotal = $371,875

Issue Date FY: 2018 ( Subtotal = $371,875 )
2018	2018	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/22/2018	NON-COMPETING CONTINUATION	$334,687
2018	2018	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	4/24/2018	NON-COMPETING CONTINUATION	$37,188
														Subtotal = $371,875

Issue Date FY: 2017 ( Subtotal = $371,875 )
2017	2017	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/13/2017	NON-COMPETING CONTINUATION	$334,687
2017	2017	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/26/2017	NON-COMPETING CONTINUATION	$37,188
														Subtotal = $371,875

Issue Date FY: 2016 ( Subtotal = $371,875 )
2016	2016	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1450 EAST DUARTE ROAD	DUARTE	CA	91010	LOS ANGELES	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/15/2016	NEW	$371,875
														Subtotal = $371,875

Grand Total All Awards = $1,859,375

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Regulation of symmetric and asymmetric cell division during brain development

Award Number: R01NS096130

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: 03/15/2016

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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