Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Nuclear Factor One (NF1) gene regulation of cortical development

Award Number: R56NS144737
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: 09/23/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2027

Group Awards By:

View Award Description

Nuclear Factor One (NF1) gene regulation of cortical development - PROJECT SUMMARY The overarching goal of this research is to elucidate the fundamental mechanisms regulating cortical development, focusing on the differentiation and maturation of neurons in the brain. Our main objective is to identify how progenitor cells in the brain are regulated to produce all the cell types required for proper circuit formation. In this project, we will study the role of nuclear factor one (NFI) genes and Tcf4 in regulating these processes. We hypothesize that these genes, which encode for transcription factors, play a central role in regulating the timing, differentiation, and maturation of cellular lineages throughout cerebral cortex development. The NFI genes NFIA, NFIB, and NFIX are each causally linked to human neurodevelopmental syndromes. These include NFIA and NFIB syndromes, and NFIX-related Malan and Marshall-Smith syndromes, collectively termed here as NFI haploinsufficiency syndromes and patients have overlapping phenotypes that include enlarged brains, corpus callosum dysgenesis and intellectual disability. We have generated mouse models for these disorders which recapitulate many of the phenotypes observed in patients. This work is therefore of direct relevance to understanding these human disorders. Nfi transcription factors are first expressed at embryonic day (E)11.5 during mouse cortical development. This coincides with this timing of the transition of neuroepithelial cells (NECs), which predominantly undergo symmetric self-renewing divisions, into radial glial cells (RGCs). RGCs divide asymmetrically, with their earliest divisions giving rise to the neurons of the preplate, the first neurons to arise in the cerebral cortex. We hypothesize that the first function of NFI transcription factors is to regulate this switch from symmetric to asymmetric cell division and that they regulate the timing and maturation of neuronal lineages that make up the different layers of the cerebral cortex in mammals. Our preliminary data indicate that NFIs might interact with another transcription factor called TCF4 in order to mediate some functions. Using Nfi and Tcf4 conditional mouse models we examine their function in regulating cell cycle dynamics, neuronal and glial differentiation, and patterning of the cortex. We examine their capacity for gene regulation using state-of-the-art methods including single-cell multiome and CUT&RUN analyses. This project is expected to identify fundamental mechanisms of brain development, specifically how NFI and TCF4 transcription factors control neural development at a more global level. This research will reveal novel insights into the molecular underpinnings of neurodevelopmental disorders, some of which were previously thought to be quite distinct, but which may be linked due to similar underlying molecular etiologies. This innovative approach combining phenotyping, genome-wide profiling, and mechanistic studies holds significant potential to direct therapeutic strategies for human neurodevelopmental disorders.


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 = $544,250 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/17/2026	NEW	$544,250
														Subtotal = $544,250

Grand Total All Awards = $544,250

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Nuclear Factor One (NF1) gene regulation of cortical development

Award Number: R56NS144737

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: 09/23/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer