Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

Investigating the molecular basis of cellular diversity in the nervous system

In plain English

AI plain-English summary

A single protein called CDX2 acts as a master switch that tells developing cells whether to become spinal cord or brainstem—and that ability disappears once cells commit to becoming neural tissue. This research tackles a fundamental gap in developmental biology: how does the early embryo generate the staggering diversity of cell types that make up the nervous system? The team has already shown that CDX transcription factors are essential for establishing spinal cord identity, but that this power is lost after neural commitment. Their preliminary data also suggests CDX influences posterior identity even before the three germ layers form. The project will now uncover the molecular mechanisms that limit CDX2 expression, how it represses brainstem fates, and its role in generating neural crest cells. This is fundamental science with no immediate clinical application. However, understanding how the nervous system builds its cellular diversity could eventually inform regenerative medicine—for instance, by providing precise instructions to turn stem cells into specific spinal cord or neural crest cell types for repair. Similar foundational work on developmental gene regulation has previously enabled lab-grown organoids and cell replacement therapies.

View original technical description
Neural induction is the process responsible for the generation of the entire nervous system. A major question in the field is how this process results in the production of diverse cell types throughout the nervous system, and how it can be applied to regenerative medicine. I recently showed that CDX transcription factors are critical to establish spinal cord fate, but that their capacity to induce spinal cord is lost following neural lineage commitment. Moreover, my preliminary data suggests that CDX factors broadly impact posterior identity in cells, prior to germ layer segregation, that is critical for the generation of different neural subtypes in the nervous system in vivo. In this proposal, the key goals are to: investigate the regulatory mechanisms limiting Cdx2 expression in cells; evaluate how CDX2 represses alternative brainstem fates for the generation of spinal cord; and test the role of CDX in the divergence of neural cells, including neural crest cells, that form distinct fates within the nervous system, in vivo. Taken together, this work will provide molecular insight into how cellular diversity is established in the mammalian nervous system and more generally throughout the body plan.

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Researchers

Amanda Fisher (EPMC Awardee)Vicki Metzis (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Multidimensional investigation of cellular dynamics and lineage relationships in the vertebrate neural tube
Challenging key concepts in neural differentiation: the role of neuromesodermal progenitors in patterning the head-to-tail axis in vertebrates
Reconstructing a Gene Regulatory Network for cell fate decisions in the sensory nervous system
The cis-regulatory logic of the ground state for neural specification
Hox genes and the diversification of neuronal Circuits.

Original classification

Sir Henry Dale Fellowship

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