The brain is a complex structure composed of several distinct tissue types, the patterning of which requires the confluence of multiple signaling networks. The neuroendocrine system represents a vital connection between the brain and body that regulates homeostasis, metabolism, mood and sexual behaviors. Disruptions in the development and regulation of this system are associated with congenital abnormalities and neuropsychiatric disorders. Here, the role of Wnt signaling in the differentiation of neuroendocrine cells in the hypothalamic-pituitary axis is investigated. We examine the effect of the apc and med12 mutations, and treatment with a Wnt-inhibitor compound on zebrafish embryos. Wnt signaling is upregulated in the apc mutant and putatively downregulated in the med12 mutant. We analyzed morphology and used in-situ hybridization to detect neuroendocrine gene expression in the pre-optic area, anterior hypothalamus, and pituitary. Our morphology data are consistent with the hypothesis that med12 acts downstream of apc to modulate transcription of Wnt-responsive genes, but suggest that this requirement is not absolute in all tissues. Our studies of brain development indicate that Med12 is required and Wnt-signaling must be suppressed for normal development of hypothalamic and pituitary cells. However, it appears that Med12 acts independently of Wnt to control the development of the cell populations investigated. Mapping the impact of Wnt signaling and the role of Med12 contributes to a better understanding of the development of neuroendocrine cells, and in what ways alterations in this pathway harm the developing organism.