Yuh-Man Sun

Yuh-Man Sun, Ph.D.

Project: NEURALDEVESTEM - Elucidating the role and molecular mechanism of Neuronatin (NNAT) in neural induction in human embryonic stem cells

Person in Charge: prof. Ing. Petr Dvořák, CSc.

Host institution: Faculty of Medicine, Masaryk university

Country of Origin: Taiwan/UK

Project duration: 24 months

Scientific panel: Life sciences


How is our brain formed? This question attracts huge attention not only from developmental biologists, but also from the biomedical field for harnessing therapeutic interventions to treat brain-related diseases. The first step of the formation of our central nervous system (CNS) is called neural induction [or development of neural stem cells (NSC)]. The general conception of neural induction is by default. The default mechanism postulates that in the absence of an extrinsic inhibitory force (i.e. BMP signalling), ectodermal cells automatically adopt neural fate. To date, default or not default, that remains a question. The emerging consensus in the mechanism underling neural induction is a combination force by inhibiting BMP pathway and activating FGF/Erk pathway, which acts extrinsically via either autocrine or paracrine manners. Since the seminal experiment carried out by Spemann and Mangold in 1924, the general concept is that neural induction is solely decided by extrinsic forces. Do intrinsic forces exist? Do they have a decisive influence on neural induction? These questions need to be answered. We have recently identified a novel intrinsic factor, Neuronatin (Nnat), which acts as a neural initiator in mouse embryonic stem (ES) cells and also promotes the neural fate in Xenopus embryos (Lin et al, submitted). This project is further to elucidate the role and the mechanism of NNAT in neural induction in human ES cells. This project will shed light on the complex networks that regulate neural specification in human ES (hES) cells and may provide paradigms for the derivation of more homogenous NSC cells from induced pluripotent stem (iPS) cells for stem cell replacement therapy.  

The ongoing project summary

  1. Established a hESC-derived neural differentiation model.
  1. Set-up a paradigm for driving hESC to differentiate towards the neural stem cells nnd then neurons.
  2. Established the time windows for the occurrence of NES and neurons, which is important for delineating the underlying mechanism of NNAT in neural fate.
  1. Obtained NNAT expression profile during hES cell-derived neural differentiation.
  2. Constructed NNAT/GFP fusion vectors.
  3. Generated NNAT-knockdown (NNAT-KD) hESC lines.
  4. Generated NNAT-overexpressing (NNAT-OE) hESC lines.
  5. Showed that NNAT interacts with SERCA2 protein.
  6. Established a group of 6 people (3 PhD students, 1 technician, 1 Master student and 1 PostDoc).
  7. Produced enough data for publication.
  8. Prepared 4 grant proposals.


A summary of the envisaged project outputs and their potential impact:

At the end of this project, I strongly believe that the data generated from this project can be published in one of the high impact Journals. The outcomes generated from this project will substantiate Nnat/NNAT as a novel regulator in neural induction not only in mouse, but also in human. The concept derived from this project will change people’s thinking in how neural induction occurs in mammals. This project will provide a new dimension in understanding the mechanisms underlying neural induction. Due to this project, there are two spin-off projects, which are carried out by two PhD students. I will present a poster at an international stem cells conference (ISSCR) ON THE 13th - 16th of June this year in Japan. Moreover, one spin-off project has produced substantial data and I am writing up a paper for publishing in a high impact factor Journal.