Publications

How neurons are generated and diversified has long puzzled developmental neurobiologists. One of the outstanding process is that it is challenging to observe the earlier and not-yet-diversified progenitors. To overcome this, we devised a neural network classifier that distinguishes neuron types by the genes they express. The classifier was then applied backwards in development: Late pupal neurons are classified according to what we know in adult, and earlier neurons are classified with the later ones. By doing so, we were able to annotate every neuron that we profiled throughout pupation. With the ability to classify pupal neurons, we identified a neuron type that is only present in the pupal stages. They decorate the margins of the medulla, and express distinct Wnt depending on whether they are on the ventral or dorsal margin, which lead us to speculate they play a role reminiscent to Cajal-Retzius cells in mammals. Additionally, we also noticed that even though optic neurons are generated over a long period spanning several days, after 20 hours after pupation, their gene expression becomes synchronized with neurons of the same type despite their ‘age’ difference.

The Drosophila visual system integrates input from 800 ommatidia and extracts different features in stereotypically connected optic ganglia. The development of the Drosophila visual system is controlled by gene regulatory networks that control the number of precursor cells, generate neuronal diversity by integrating spatial and temporal information, coordinate the timing of retinal and optic lobe cell differentiation, and determine distinct synaptic targets of each cell type. In this chapter, we describe the known gene regulatory networks involved in the development of the different parts of the visual system and explore general components in these gene networks. Finally, we discuss the advantages of the fly visual system as a model for gene regulatory network discovery in the era of single-cell transcriptomics.

Amyotrophic lateral sclerosis is a neurodegenerative disease that causes progressive paralysis that is lethal and incurable to date. In this article, we discovered a developmentally critical microRNA cluster, mir-17~92, plays a role in the vulnerability of spinal motor neurons and supplementing this microRNA cluster can prolong the life expectancy in a mouse disease model.

In this article, we demonstrated that a long non-coding RNA, Meg3, is required to establish the boundary between two genes that mark spinal motor neurons from different body segments. To suppress the expression of caudal genes from expressing in rostral segments, Meg3 forms a complex with PRC2 to suppress them, the catalytic complex that marks histone with repressive modificication H3K27me3.