# Transcriptional regulation of post-embryonic neuronal maturation

> **NIH NIH K99** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2020 · $132,543

## Abstract

PROJECT SUMMARY/ABSTRACT
 During the complex and intricately-timed sequence of nervous system development and maturation,
significant and persistent disruptions to the dynamic regulatory process through genetic and environmental
risks can result in neurodevelopmental disorders. Neuroscience research has contributed much to our
understanding of early neural development in the embryonic and perinatal periods including neuronal
specification, neuronal migration, axonal guidance/outgrowth, and synaptogenesis. The period from early
post-natal life to young adulthood is equally critical for proper development of the mature brain, as extensive
structural and behavioral plasticity are observed during these periods. However, much less is known about the
molecular regulatory mechanisms underlying neuronal maturation during post-natal development. In the first
part of my post-doctoral work, I developed and optimized a method to isolate single neuron types for genomics
profiling. Using this method, in combination with the genetic amenability of the C. elegans system, I will
profile the transcriptome and chromatin accessibility of single neuron types throughout early post-natal
development to young adulthood (Aim 1). In Aim 2, using the profiling data from Aim 1 as an entry point, I
will take a 2-pronged approach to identify novel regulators of neuronal maturation. First, I will co-develop and
implement bioinformatics tools to extract common cis-regulatory motifs from developmentally regulated genes
and predict candidate transcriptional regulators. Second, using validated developmentally-regulated gene
reporters in Aim 1, I will conduct unbiased forward genetic screens to identify novel regulators of neuronal
maturation. In Aim 3, I will use advanced neurotechnology tools to examine the role of environmental stimuli
(sensory-induced neuron activity) on neuronal maturation. First, I will examine how acute and chronic inhibition
of activity in target neurons, during different developmental windows, affects single-neuron developmental
transcriptomes and chromatin accessibility. In addition, the interaction between pathways regulating neuronal
maturation through environmentally-induced activity versus intrinsic genetic mechanisms will be examined
using approaches as in Aim 2. The proposed research will increase our understanding of the genetic and
environmental regulatory mechanisms underlying normal post-natal neurodevelopment, improve our
understanding of the etiology of neurodevelopmental disorders, and reveal novel therapeutic targets.
 The training phase of the award, conducted in the laboratory of Dr. Oliver Hobert and under the co-
mentorship of Dr. Harmen Bussemaker and Dr. Stavros Lomvardas at Columbia University, outlines a
comprehensive plan for the acquisition of technical and professional skills that will enable my transition to an
independent research position. The successful completion of this project will provide a platform for future
experiments ...

## Key facts

- **NIH application ID:** 9922937
- **Project number:** 5K99HD098371-02
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Haosheng Sun
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $132,543
- **Award type:** 5
- **Project period:** 2019-05-01 → 2021-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922937

## Citation

> US National Institutes of Health, RePORTER application 9922937, Transcriptional regulation of post-embryonic neuronal maturation (5K99HD098371-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9922937. Licensed CC0.

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