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Regulation of Hoxa1 Gene Expression in Mouse Embryonic Stem Cells

Award Number: R15NS091949
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: 04/01/2015
PERIOD OF PERFORMANCE END DATE: 03/31/2019

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Regulation of Hoxa1 Gene Expression in Mouse Embryonic Stem Cells - ¿ DESCRIPTION (provided by applicant): Regulation of Hoxa1 Gene Expression in Mouse Embryonic Stem Cells The homeobox (Hox) family of transcription factors comprises important regulators of embryonic patterning and organogenesis. Inactivation in mice of both alleles of the Hoxa1, a Hox family member, results in numerous developmental defects, including hindbrain deficiencies and abnormal skull ossification, and ultimately, in neonatal death. These observations emphasize the importance of this gene in the proper development of the early brain and neural crest- derived structures. In humans, mutations in this gene have been described in association with various Central Nervous System (CNS) disorders and its overexpression has been associated with cancer development. Thus, a strict control of Hoxa1 gene expression is required for proper cellular function and embryonic development. Although the relevance of Hoxa1 during embryonic development has been recognized for over two decades, little is known about the factors that regulate the expression of this important TF. In this work, we present preliminary data that suggests a role for the retinoic acid receptor beta 2 (RARb2) as a negative regulator of Hoxa1 gene expression in mouse Embryonic Stem (ES) cells. Furthermore, we have performed ChIP-on-chip analyses for Hoxa1 and identified a putative Hoxa1 binding site in the Hoxa1 coding region, which suggests the presence of a novel autoregulatory mechanism for this TF. Thus, these preliminary results form the basis of the specific aims proposed in this project. Specific Aim 1 will investigate the regulation of Hoxa1 gene expression at the transcriptional level. Specific Aim 2 will investigate the effect of factors that regulate Hoxa1 expression at the posttranscriptional level. The mechanism of Hoxa1 feedback loop of gene regulation will be investigated in Specific Aim 3. In summary, the goal of the proposed study is to shed light on the molecular mechanism by which the expression of Hoxa1 is regulated in mouse ES cells. The results from these studies will be of relevance to the areas of Developmental Biology, Organ and Tissue Replacement, and Cancer Research, among others.


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: 2019 ( Subtotal = -$48,831 )
2019	2015	SOUTHERN UNIVERSITY AND ANM COLLEGE SYSTEM	730 HARDING BLVD	BATON ROUGE	LA	70807	EAST BATON ROUGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/10/2019	NEW	-$48,831
														Subtotal = -$48,831

Issue Date FY: 2015 ( Subtotal = $331,560 )
2015	2015	SOUTHERN UNIVERSITY AND A&M COLLEGE	SOUTHERN BRANCH, P.O.BOX 12596	BATON ROUGE	LA	70813	EAST BATON ROUGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/21/2015	NEW	$331,560
														Subtotal = $331,560

Grand Total All Awards = $282,729

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Regulation of Hoxa1 Gene Expression in Mouse Embryonic Stem Cells

Award Number: R15NS091949

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: 04/01/2015

PERIOD OF PERFORMANCE END DATE: 03/31/2019

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