Tal2 is required for generation of GABAergic neurons in the zebrafish midbrain.

ABSTRACT

BACKGROUND: In the zebrafish midbrain, GABAergic neurons develop from precursors located in the nucleus of the medial longitudinal fasciculus (nMLF). However, the precise mechanisms that underline generation of the nMLF GABAergic neuron are poorly understood. RESULTS: GABAergic neurons in the nMLF co-express transcription factors tal2, gata2a, gata3, and nkx1.2lb. The Nodal-related gene and shh signaling are required for differentiation of nMLF GABAergic neuron precursors. Tal2 is important for nMLF GABAergic neurogenesis. Disruption of Tal2, embryos completely lack the GABA-synthesizing enzyme glutamic acid decarboxylase 67 gene (gad67) expressing cells in the nMLF, and the whole nkx1.2lb expressing cells in the midbrain. Although almost all tal2-expressing cells in the diencephalon and/or nMLF are gata2a- and gata3-positive, simultaneous knockdown of gata2a and gata3 does not affect either tal2 or gad67 expression. CONCLUSIONS: In the zebrafish midbrain, expression of tal2, gata2a, and/or gata3 is independent of each other. The function of gata2a and gata3 is dispensable for generation of GABAergic neuron in the nMLF. This suggests that the functional connections of the regulatory genes leading to generation of nMLF GABAergic neurons have diverged between mouse and zebrafish.