# A Fully Patterned Human Neural Tube Model Using Microfluidics

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $507,741

## Abstract

Project Summary
A Fully Patterned Human Neural Tube Model Using Microfluidics
The development of vertebrate central nervous system (CNS) begins with the formation of neural tube (NT)
and its regional patterning to generate neuronal subtypes along the rostral (R)-caudal (C) and dorsal (D)-
ventral (V) axes. Regional patterning of the human NT is a tightly regulated process, deviation from which can
result in neurodevelopmental disorders and may lead to distinct neurological and psychiatric diseases later in
life. Regional patterning of the human NT remains incompletely understood due to limited access to human
embryonic tissues. Animal models have been instrumental in understanding the development of human CNS
and associated disorders. However, they are limited in revealing some fundamental aspects of development,
genetics, pathology, and disease mechanisms that are unique to humans. Stem cell-based in vitro models of
human nervous system development, including neural organoids and bioengineered NT development models,
are emerging as promising experimental tools. However, none of the current stem cell-based neural
development models is capable of recapitulating neural patterning along two orthogonal axes in a 3D tubular
geometry, the hallmark of NT patterning in vivo. Furthermore, the existing neural development models only
recapitulate certain aspects of the development of either human brain or spinal cord regions but not both.
 In our preliminary study, we have successfully leveraged the developmental potential and self-
organizing property of human pluripotent stem cells (hPSCs) in conjunction with microfluidics to develop the
first of its kind, synthetic, fully patterned human NT model. Using this microfluidic platform, exogenous
morphogen gradients along two orthogonal axes can be established to achieve regional patterning of the
microfluidic human NT-like structure along both the R-C and D-V axes, in both brain-like and spinal cord-like
regions. This microfluidic patterned human NT-like structure exhibits many hallmarks of NT development,
including a tubular geometry, a single continuous central lumen enclosing by neuronal progenitor cells,
patterned expression of canonical R-C and D-V regional markers including HOX genes, and the emergence of
neural mesodermal progenitors and the isthmic organizer. Thus, the development of the microfluidic human
NT-like structure closely mimics NT development, offering for the first time an in vivo-like tissue architecture
with consistent spatiotemporal cell differentiation and organization.
 The goal of this R01 research is to develop this exciting microfluidic human NT-like model (Aim 1) and
leverage its technical advantages to study the roles of different exogenous morphogen signals in neural
patterning (Aim 2 & 3). Genetic perturbations and lineage tracing assays will be conducted to study human
neural mesodermal progenitor development (Aim 2). In Aim 3 we further aim to achieve D-V patterned human
NT-l...

## Key facts

- **NIH application ID:** 10906944
- **Project number:** 5R01NS129850-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Jianping Fu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $507,741
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906944

## Citation

> US National Institutes of Health, RePORTER application 10906944, A Fully Patterned Human Neural Tube Model Using Microfluidics (5R01NS129850-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10906944. Licensed CC0.

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