# Investigating molecular mechanisms and function of tanycyte-derived neurogenesis in the postnatal hypothalamus

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2022 · $46,752

## Abstract

PROJECT SUMMARY
 In recent years, evidence now shows that tanycytes possess the ability to generate neurons in the
postnatal hypothalamus. Tanycytes are radial glial cells that closely resemble neural progenitors in both
morphology and gene expression profiles. While dietary and hormonal cues can regulate tanycyte-derived
neurogenesis, the overall levels of tanycyte proliferation and tanycyte-derived neurogenesis are low and
virtually undetectable in adult mice. The molecular mechanisms controlling neurogenic competence in
tanycytes, and the precise physiological function of tanycyte-derived neurons remains poorly defined.
Identifying molecular mechanisms that stimulate tanycyte-derived neurogenesis, to promote differentiation of
tanycyte-derived neurons that modulate body weight and metabolism, is a new potential therapeutic for treating
obesity and metabolic disorders such as type II diabetes.
 Recently, studies from the Blackshaw lab have identified the Nuclear Factor One (Nfi) family transcription
factors (TFs), Nfia/b/x, as playing a critical role in regulating neurogenic competence in hypothalamic
tanycytes. Under normal dietary conditions in male mice, Nfia/b/x-deficient tanycytes show enhanced
proliferation and neurogenesis. Single-cell RNA-sequencing analysis of Nfia/b/x-deficient tanycytes and
tanycyte-derived cells indicates that a substantial fraction of all tanycyte-derived neurons are GABAergic
subtypes. A subset of these GABAergic neurons expresses the Leptin receptor (Lepr) and responds to leptin.
The Blackshaw lab has also shown that tanycyte-derived neurons survive, integrate into hypothalamic circuits,
and fire spontaneous action potentials. By analyzing genes differentially expressed between control and
Nfia/b/x-deficient tanycytes, we have shown that Shh and Wnt signaling is upregulated in tanycytes following
loss of Nfia/b/x. We also observed the downregulation of the Notch pathway in Nfia/b/x-deficient tanycytes.
During development, Shh and Wnt pathways promotes neurogenesis in the hypothalamus. While Notch
signaling pathway promote quiescence in retinal Müller glia and cortical astrocytes. Given these findings, I
hypothesize that neurogenic competence in tanycytes is actively suppressed in the postnatal
hypothalamus after neurogenesis and, hypothesize that tanycyte-derived neurons regulate body
weight homeostasis and metabolism. To address these hypotheses, I propose the following two Aims:
AIM 1: To investigate extrinsic regulators that positively or negatively control tanycyte-derived
neurogenesis in the juvenile and young adult hypothalamus. This work will identify molecular mechanisms
and gene regulatory networks that positively or negatively regulate tanycyte-derived neurogenesis in the
postnatal hypothalamus.
AIM 2: To determine the role of tanycyte-derived neurons on bodyweight homeostasis and metabolism.
These studies will provide key insights into the physiological function of tanycyte-derived neurons in controlli...

## Key facts

- **NIH application ID:** 10465440
- **Project number:** 1F31DK132944-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Leighton Hosea Duncan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465440

## Citation

> US National Institutes of Health, RePORTER application 10465440, Investigating molecular mechanisms and function of tanycyte-derived neurogenesis in the postnatal hypothalamus (1F31DK132944-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10465440. Licensed CC0.

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