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.