# A TAP63 TRANSCRIPTIONAL AXIS CONTRIBUTES TO THE SEXUAL DIMORPHISM IN POMC NEURON FUNCTIONS AND ENERGY HOMEOSTASIS

> **NIH NIH K01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $38,913

## Abstract

Obesity is recognized as a major health issue due to its high prevalence and strong association with diabetes
and other metabolic disorders. Female animals are more resistant to obesity than males, but the mechanisms
for this sexual dimorphism remain elusive. In my previous studies, I first screened body weight-regulatory neural
populations and found that pro-opiomelanocortin (POMC) neurons in female mice fire more rapidly than male
POMC neurons, and female mouse brains express higher POMC transcripts. Further, these sex differences in
POMC neurons were associated with higher expression levels of TAp63 (a transcription factor) and SRC1
(steroid receptor coactivator-1, a transcriptional coactivator) in female POMC neurons than in male counterparts.
Pilot studies showed that TAp63 can activate POMC gene expression in cultured cells. Further, SRC1 mRNA
was significantly reduced by TAp63 deletion in female mice, suggesting that SRC1 is a transcription target of
TAp63. Importantly, deletion of TAp63 or SRC1 only in POMC neurons in mice regulates body weight in a
sexually dimorphic fashion. Together, I developed a hypothesis that an estrogen-TAp63-SRC1 transcriptional
axis contributes to the sexual dimorphism in POMC neuron functions and energy homeostasis. I will generate
mice that lack TAp63 or SRC1 in POMC neurons, and characterize energy homeostasis and POMC neuron
functions (activity and gene expression profile) among male mice, female mice with or without intact ovary (OVX-
V), and female without intact ovary but with estrogen supplement (OVX-E). I will also examine whether estrogen
stimulates TAp63 expression and whether TAp63 stimulates SRC1 expression. The proposed studies represent
logical extensions to my previous work, and will advance our understanding about the fundamental biology for
sex differences in body weight control, which may facilitate the development of gender-specific therapeutic
strategies for obesity and associated metabolic diseases. In addition, this project will provide an ideal training
opportunity to prepare me for an independent research career focusing on transcriptional mechanisms in the
hypothalamus and their roles in metabolic control.

## Key facts

- **NIH application ID:** 10436077
- **Project number:** 3K01DK119471-03S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Chunmei Wang
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,913
- **Award type:** 3
- **Project period:** 2019-07-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436077

## Citation

> US National Institutes of Health, RePORTER application 10436077, A TAP63 TRANSCRIPTIONAL AXIS CONTRIBUTES TO THE SEXUAL DIMORPHISM IN POMC NEURON FUNCTIONS AND ENERGY HOMEOSTASIS (3K01DK119471-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10436077. Licensed CC0.

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