# Yolk Sac MicroRNAs Regulate Brain Development

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2024 · $48,974

## Abstract

PROJECT SUMMARY/ABSTRACT
 In the United States alone, over 600,00 babies are born each year that will go on to suffer
from a neurodevelopmental disorder including autism spectrum disorders, attention deficit
disorder, and other intellectual disabilities. A major obstacle to preventing and treating
neurodevelopmental disorders is that the first steps of brain development occur often before the
pregnancy is discovered. The first step of brain development, in which the bilateral halves of the
neuroepithelium converge to form the neural tube, is a period of rapid morphogenesis that creates
heightened metabolic demand. The neural tube is sensitive to changes in maternal metabolism
and disease states such as maternal hyperglycemia and folate deficiency have been linked to
neurological disability. Neural tube closure occurs before the placenta is established and nutrients
are instead absorbed and processed by the yolk sac. How maternal-fetal nutrient exchange is
regulated during neural tube closure is not well understood. The yolk sac also generates cells that
migrate into the early brain to control neuronal differentiation during neural tube closure. It is
poorly understood how yolk sac-derived cells regulate development of the neuroepithelium.
MicroRNA function in the yolk sac is critical for embryonic growth, suggesting a role in maternal-
fetal nutrient exchange. Whether microRNAs regulate maternal-fetal nutrient exchange across
the yolk sac remains unknown. We find that miR-290 is robustly expressed in the yolk sac
endoderm and loss of miR-290 in hyperglycemic pregnancies results in a failure of neural tube
closure. Further, we find miR-290 expressing yolk sac-derived blood cells at the basal
neuroepithelium. Upon miR-290 deletion we find a reduction in yolk sac-derived blood cells in the
embryonic cranial region and a significant reduction of neurogenesis. We hypothesize that miR-
290 regulates maternal-fetal nutrient exchange across the yolk sac and that yolk sac-derived
blood cells are required for proper neuroepithelial development. The proposed work will uncover
how the interaction between the yolk sac and developing embryo facilitates brain development
and will be critical for preventing intellectual disability. The major goals of this study are to identify
how miR-290 regulates development and function of the yolk sac during neural tube closure and
determine how yolk sac-derived cells regulate neuroepithelial development. Understanding how
the yolk sac controls neural tube closure and early brain development will present a new
therapeutic approach to prevent neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10935958
- **Project number:** 5F31HD110243-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Rachel Anne Keuls
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-08-17 → 2025-08-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935958

## Citation

> US National Institutes of Health, RePORTER application 10935958, Yolk Sac MicroRNAs Regulate Brain Development (5F31HD110243-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10935958. Licensed CC0.

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