The development of specialized and properly wired neuronal networks is crucial for the function of nervous system. Abnormal neuronal specification and wiring lead to neurological disorders or lethality. Using diencephalic habenula nuclei (HA) and their connections to the interpeduncular nucleus (IPN) as a model (Figure 1), I have studied how HA are generated and how habenular axons recognize their targets during zebrafish embryonic development. Utilizing different approaches such as data mining, molecular manipulation and laser ablation, I found that Neuropilin 1a (Nrp1a) positive habenular neurons extend their axons onto the dorsal IPN by responding to attractive guidance cues Semaphorin 3D (Sema3D) (Figure 2). Utilizing chemical mutagenesis and in situ hybridization screen, I found that the novel Golgi protein Wntless (Wls) plays a critical role during habenula neurogenesis, presumably by controlling the expression of proneural gene neurogenin 1 (ngn1) (Figure 3).
Currently I am investigating the mechanisms of how HA axons correctly navigate to their targets, how Wls influence HA neurogenesis, and how different habenular neurons adopt their individual identities during the generation of HA-IPN circuit. Understand the factors and mechanisms that control the development of HA-IPN circuit in zebrafish will quickly advance our knowledge of this important neural circuit in all vertebrates and may shed light on human conditions involving altered neuronal generation and axonal connectivity.
Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish.
Lu S, Lyu Z, Wang Z, Kou Y, Liu C, Li S, Hu M, Zhu H, Wang W, Zhang C, Kuan YS, Liu YW, Chen J, Tian J
Theranostics (2021)
Three-dimensional multi-gene expression maps reveal cell fate changes associated with laterality reversal of zebrafish habenula.
Wang GT, Pan HY, Lang WH, Yu YD, Hsieh CH, Kuan YS
Journal of Neuroscience Research (2021)
Control of Wnt5b secretion by Wntless modulates chondrogenic cell proliferation through fine-tuning fgf3 expression.
Wu BT, Wen SH, Hwang SP, Huang CJ, Kuan YS
Journal of cell science (2015)
Inhibition of Escherichia coli respiratory enzymes by short visible femtosecond laser irradiation.
Lu CH, Lin KH, Hsu YY, Tsen KT, Kuan YS
Journal of Physics D-Applied Physics (2014)
Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling."
Liao WH, Cheng CH, Hung KS, Chiu WT, Chen GD, Hwang PP, Hwang SP, Kuan YS, Huang CJ
Cellular and molecular life sciences : CMLS (2013)
Drosophila Suppressor of sable protein (Su(s)) promotes degradation of aberrant and transposon-derived RNAs.
Kuan, Y.S., Brewer-Jensen, P., Bai, W.L., Hunter, C., Wilson, C.B., Bass, S., Abernethy, J., Wing, J.S. and Lillie L. Searles.
Molecular and cellular biology (2009)
Neuropilin asymmetry mediates a left-right difference in habenular connectivity.
Kuan YS, Yu HH, Moens CB, Halpern ME
Development (2007)
Selective asymmetry in a conserved forebrain to midbrain projection.
Kuan YS, Gamse JT, Schreiber AM, Halpern ME
Journal of experimental zoology. Part B. Molecular and developmental evolution (2007)