Neural plate progenitors give rise to both anterior and posterior pituitary cells

Abstract

The pituitary is the master neuroendocrine gland, which regulates body homeostasis. It consists of the anterior pituitary/adenohypophysis (AH), which harbors hormones producing cells and the posterior pituitary/neurohypophysis (NH), which relays the direct passage of hormones from the brain to the periphery. It is widely accepted that the AH originates from the oral ectoderm (Rathkes pouch) whereas the neural ectoderm contributes to the NH. Using single cell transcriptomics of the zebrafish pituitary we characterized cyp26b1-positive pituicyte of the NH and prop1-positive adenohypophyseal progenitors. We found that these cell types expressed common markers implying lineage relatedness. Genetic tracing revealed that in contrast to the prevailing dogma, neural plate precursors of both zebrafish (her4.3+) and mouse (Sox1+) contribute to both the neurohypophyseal and adenohypophyseal cells. We further show that pituicytes and prop1+ progenitors reside in close anatomical proximity and pituicyte-derived RA-degrading enzyme Cyp26b1 fine-tunes differentiation of prop1+ progenitors into hormone-producing cells. These results challenge the notion that AH cells are exclusively derived from non-neural ectoderm and demonstrate that a cross-talk between neuro- and adeno-hypophyseal cells fine-tunes the development of pituitary neuroendocrine cells.