Tuesday, April 16, 2024 4/16/2024

MOLECULAR ANALYSIS OF HINDBRAIN DEVELOPMENT

Award Number: R01NS038183
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Formation of the CNS during embryogenesis requires the de novo initiation of neural gene expression in embryonic ectoderm. E.g., the Hoxb1a and Hoxb1b transcription factors (TFs) are required for zebrafish hindbrain development, but it is unclear how they activate gene expression. In particular, embryonic chromatin is compacted, making regulatory elements inaccessible to most TFs. We find that Prep and Pbx (two TFs identified as cofactors to Hox proteins) occupy genetic loci prior to zygotic genome activation – many hours before Hox proteins are active and well before hindbrain development is initiated. Also, Prep:Pbx occupied sites co-localize with binding sites for the NFY TF. We hypothesize that maternally deposited Prep:Pbx cooperates with NFY to open chromatin at hindbrain genes. This process exposes binding sites for hindbrain-specific TFs (e.g. Hox proteins) to drive gene expression in the hindbrain. There are three aims of our proposed work: First we will disrupt Prep:Pbx and NFY function to determine if they modulate the chromatin state. Second, we will determine if Prep:Pbx-mediated chromatin changes promote binding by Hoxb1b to create hindbrain- specific enhancers. Lastly, we will determine how such enhancers drive hindbrain-specific gene expression. This work is relevant for several reasons. First, it is important to understand hindbrain development per se (as defects give rise to ataxias etc.). Second, our results will be applicable to understanding hox function in general, which is important since other hox genes are involved in hindbrain development (and many other cell fate decisions). Additionally, prep and pbx are proto-oncogenes and it is likely that their ability to drive de novo gene expression will explain some of their oncogenic potential. Lastly, our experiments will show how genes can be activated in inaccessible chromatin. This will be applicable to targeted differentiation/reprogramming of stem or precursor cells – hence our work will also inform efforts to generate specific cell types for clinical applications.


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: 2024 ( Subtotal = $460,205 )
2024	2024	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	1/9/2024	COMPETING CONTINUATION	$460,205
														Subtotal = $460,205

Issue Date FY: 2022 ( Subtotal = $369,767 )
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	11/8/2021	NON-COMPETING CONTINUATION	$332,792
2022	2022	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	23	3/29/2022	NON-COMPETING CONTINUATION	$36,975
														Subtotal = $369,767

Issue Date FY: 2021 ( Subtotal = $369,767 )
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	22	2/4/2021	NON-COMPETING CONTINUATION	$36,975
2021	2021	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	22	10/30/2020	NON-COMPETING CONTINUATION	$332,792
														Subtotal = $369,767

Issue Date FY: 2020 ( Subtotal = $369,767 )
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	21	5/8/2020	NON-COMPETING CONTINUATION	$0
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	21	2/10/2020	NON-COMPETING CONTINUATION	$36,975
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	12/6/2019	NON-COMPETING CONTINUATION	$332,792
2020	2020	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	21	1/14/2020	NON-COMPETING CONTINUATION	$12,918
2020	2018	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	19	1/14/2020	NON-COMPETING CONTINUATION	-$12,918
														Subtotal = $369,767

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2018	REGENTS OF THE UNIVERSITY OF COLORADO, THE	13001 E 17TH PLACE F428	AURORA	CO	80045	ADAMS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	20	9/14/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$75,450
2019	2018	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE NORTH	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	9/14/2019	NON-COMPETING CONTINUATION	-$75,450
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $398,555 )
2018	2018	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	7/26/2018	NON-COMPETING CONTINUATION	$398,555
														Subtotal = $398,555

Issue Date FY: 2017 ( Subtotal = $406,805 )
2017	2017	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	9/22/2017	COMPETING CONTINUATION	$406,805
2017	2016	UNIVERSITY OF MASSACHUSETTS	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	17	9/22/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $406,805

Issue Date FY: 2016 ( Subtotal = $359,844 )
2016	2016	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	6/3/2016	EXTENSION WITH OR WITHOUT FUNDS	$359,844
														Subtotal = $359,844

Issue Date FY: 2015 ( Subtotal = $359,844 )
2015	2015	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	5/17/2015	NON-COMPETING CONTINUATION	$359,844
														Subtotal = $359,844

Issue Date FY: 2014 ( Subtotal = $356,246 )
2014	2014	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	15	5/20/2014	NON-COMPETING CONTINUATION	$356,246
														Subtotal = $356,246

Issue Date FY: 2013 ( Subtotal = $347,250 )
2013	2013	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	5/24/2013	NON-COMPETING CONTINUATION	$347,250
														Subtotal = $347,250

Issue Date FY: 2012 ( Subtotal = $359,844 )
2012	2012	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	4/20/2012	COMPETING CONTINUATION	$359,844
														Subtotal = $359,844

Issue Date FY: 2011 ( Subtotal = $348,359 )
2011	2011	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	6/24/2011	NON-COMPETING CONTINUATION	$348,359
														Subtotal = $348,359

Issue Date FY: 2010 ( Subtotal = $351,915 )
2010	2010	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	5/25/2010	NON-COMPETING CONTINUATION	$351,915
														Subtotal = $351,915

Issue Date FY: 2009 ( Subtotal = $355,469 )
2009	2009	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	6/3/2009	NON-COMPETING CONTINUATION	$355,469
														Subtotal = $355,469

Issue Date FY: 2008 ( Subtotal = $355,469 )
2008	2008	UNIVERSITY OF MASSACHUSETTS	406 GOODELL BLDG, BOX 33210	AMHERST	MA	01003	HAMPSHIRE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	2/4/2008	COMPETING CONTINUATION	$355,469
														Subtotal = $355,469

Issue Date FY: 2006 ( Subtotal = $295,001 )
2006	2006	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	4/5/2006	NON-COMPETING CONTINUATION	$295,001
														Subtotal = $295,001

Issue Date FY: 2005 ( Subtotal = $302,100 )
2005	2005	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	2/24/2005	NON-COMPETING CONTINUATION	$302,100
														Subtotal = $302,100

Issue Date FY: 2004 ( Subtotal = $302,100 )
2004	2004	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	2/26/2004	NON-COMPETING CONTINUATION	$302,100
														Subtotal = $302,100

Issue Date FY: 2003 ( Subtotal = $325,850 )
2003	2003	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/23/2003	COMPETING CONTINUATION	$325,850
														Subtotal = $325,850

Issue Date FY: 2002 ( Subtotal = $203,635 )
2002	2002	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL AT WORCESTER	55 LAKE AVENUE NORTH	WORCESTER	MA	01605	WORCESTER	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/20/2001	NON-COMPETING CONTINUATION	$203,635
														Subtotal = $203,635

Grand Total All Awards = $7,603,917

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MOLECULAR ANALYSIS OF HINDBRAIN DEVELOPMENT

Award Number: R01NS038183

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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