# Investigating the role of fatty acid metabolism in melanocyte differentiation: Insights into the metabolic requirements of development

> **NIH NIH F31** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $5,496

## Abstract

PROJECT SUMMARY
Melanocytes are a key cell lineage in the skin and are required for skin pigmentation. Defects in melanocyte
development and function can lead to pigmentation disorders causing hypo or hyperpigmentation as well as one
of the most deadly forms of skin cancer, melanoma. Many of the transcriptional and signaling events which cause
these diseases have been explored, however, there has been little investigation into the role of the metabolic
environment and intracellular metabolic state of the melanocyte during development. Recent work from our lab
has demonstrated that during melanoma progression, adipocytes in the tumor microenvironment can transfer
fatty acids to the melanoma cells, promoting invasion. This raises the question of whether fatty acid uptake plays
a role in normal melanocytes. Our preliminary data suggests that melanocytes require extrinsic uptake of fatty
acids through Fatty Acid Transport Proteins (FATPs) for proper differentiation. In Aim 1, we will investigate the
relative importance of fatty acid uptake and de novo fatty acid synthesis in the melanocyte. We will
compare multiple mechanisms of fatty acid uptake as well as fatty acid synthesis to determine which play the
most important role in melanocyte development and pattern formation. We will also dissect in a stage specific
manner when these pathways are required by the melanocyte during differentiation using genetic perturbations.
We hypothesize that the importance of fatty acids in the melanocyte reflects certain lineage specific needs,
including high levels of fatty acids to support phospholipid synthesis and dendrite formation. In Aim 2 we will
examine the importance of fatty acids as building blocks for phospholipid synthesis relative to a
requirement for fatty acid breakdown through b-oxidation. There is evidence for the importance of
phospholipid synthesis in other dendritic cell types. Because melanocytes also form extensive dendrites which
are critical for proper pigmentation we will dissect the importance major phospholipid synthesis pathways to the
melanocyte in a stage specific manner. Conversely, melanocytes might break down fatty acids as a source of
ATP to support cell proliferation and migration. We will also determine the role b-oxidation in melanocyte
development by targeting key proteins in this pathway in a stage specific manner. We will assess the effects of
these genetic perturbations on energy production and melanocyte development. To perform these studies we
will primarily rely on zebrafish as an in vivo model of melanocyte development. We will use stage specific
promoters for the neural crest, melanoblast, and melanocyte to generate stable germline transgenics. Using a
combination of genetic methods and image analysis we will investigate the role of fatty acid and lipid metabolism
in melanocyte development. When appropriate, we will also apply an in vitro model of melanocyte development,
based on the differentiation of melanocytes from ...

## Key facts

- **NIH application ID:** 10862636
- **Project number:** 5F31AR079215-04
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Eleanor May Johns
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $5,496
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862636

## Citation

> US National Institutes of Health, RePORTER application 10862636, Investigating the role of fatty acid metabolism in melanocyte differentiation: Insights into the metabolic requirements of development (5F31AR079215-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10862636. Licensed CC0.

---

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