# Distal enhancers controlling motor neuron gene expression program

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $524,346

## Abstract

Transcriptional programming of cell identity is gaining importance at both the basic developmental and the
clinical levels. While the phenomenology of cell programming and reprogramming by forced expression of
transcription factors is well described, the mechanisms of action of programming factors or the sequence of
regulatory events resulting in a cell adopting a new identity are largely unknown. We are combining the
strengths of stem cell biology with genomic and computational approaches to map the process of
transcriptional programming of spinal motor neuron (MN) identity at a deep molecular level. We have
developed efficient methods for the induction of MN identity in differentiating embryonic stem cells (ESCs) by
the expression of programming transcription factors. Using this system, we combine biochemical, genomic,
and computational analysis to address following questions: i) how is Isl1 recruited to transient enhancers in
postmitotic motor neurons; ii) does Isl1 control enhancer activation; iii) are Klf factors bound to MN enhancers
important for mediator and cohesin recruitment; iv) what motifs and factors coordinate interactions between
distal and proximal MN-specific enhancers; v) can we infer the mechanisms controlling MN subtype
specification and maturation by studying cell type and cell stage-specific regulatory regions in primary MNs.
Together these studies will provide fundamental insight into the developmental processes underlying the
specification of defined cell identity in the complex vertebrate nervous system and will provide a novel and
efficient source of MNs for disease modeling, functional analysis, and drug discovery.

## Key facts

- **NIH application ID:** 10074601
- **Project number:** 5R01NS109217-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Hynek Wichterle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $524,346
- **Award type:** 5
- **Project period:** 2018-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074601

## Citation

> US National Institutes of Health, RePORTER application 10074601, Distal enhancers controlling motor neuron gene expression program (5R01NS109217-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074601. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*