Molecular Physiology of Pituitary Development: Signaling and Transcriptional Networks

Abstract

The pituitary gland is a central endocrine organ regulating basic physiological functions, including growth, the stress response, reproduction, metabolic homeostasis, and lactation. Distinct hormone-producing cell types in the anterior pituitary arise from a common ectodermal primordium during development by extrinsic and intrinsic mechanisms, providing a powerful model system for elucidating general principles in mammalian organogenesis. The central purpose of this review is to inspect the integrated signaling and transcriptional events that affect precursor proliferation, cell lineage commitment, terminal differentiation, and physiological regulation by hypothalamic tropic factors.

How to make a teleost adenohypophysis: Molecular pathways of pituitary development in zebrafish

“…In addition, there is some, although less striking dorso-ventral polarity of the zebrafish adenohypophysis. For instance, gonadotropes are preferentially located ventral of thryrotropes and somatotropes M a n u s c r i p t 7 of the posterior PD (Glasgow et al, 1997, Nica et al, 2004, consistent with the ventral location of gonadotropes in Rathke's pouch, the AH anlage of the mouse ( (Treier et al, 1998, Zhu et al, 2005, Zhu et al, 2007. While the arrangement of PD in anterior and PI in posterior regions of the AH is conserved between zebrafish and mouse, the mouse PD per se does not display an apparent intrinsic anterior-posterior, but rather a dorso-ventral polarity (Treier et al, 1998, Zhu et al, 2005.…”

“…Six of them encode components of Admittedly, thus far, the forward genetics approach did not identify as many new players of pituitary development as we had hoped. Rather, most identified regulators or pathways had already been known based on the wonderful work carried out in mouse (Zhu et al, 2007). Just in one case (ascl1a), zebrafish genetics provided first functional information on a transcription factor family that had not been studied much in this context thus far, since in mouse, the corresponding mutants did not show a pituitary phenotype, most likely due to functional redundancies.…”

“…In mouse, Pit1 expression requires the concerted action of Wnt/-catenin signaling and the paired-like homeodomain transcription factor Prop1, which also affects the Notch pathway (Raetzman et al, 2004, Olson et al, 2006, Zhu et al, 2007. However, also here, it is not understood how these pathways might contribute to Pit1's spatial restriction, while in zebrafish, neither Prop1 nor canonical Wnt genes have been described in the context of AH development at all.…”

At least two expressed genes for transcription factors Pitx2 and Rpx are present in common carp and are upregulated during winter acclimatization

“…This acclimatization 44 process occurs through a cyclical reprogramming of molecular processes, involving 45 in common carp (Cyprinus carpio) the modulation of transcriptional and translational 46 events in various tissues (Krauskopf et al, 1988;Figueroa et al, 1994; Goldspink et 47 in loss of lineages depending on the related factor Prop1 indicating that a tight 92 control of the opposing actions of these two factors is required for normal 93 development in mouse. Prop1 is required for onset of Pit1 expression and thus for 94 differentiation of the entire Pit1 lineage (Zhu et al, 2007). 95…”

“…In good correlation with these observations, expression of the 60 main regulator of these genes, the pituitary-specific transcription factor Pit1 is 61 strongly increased during acclimatization of the common carp (Cyprinus carpio) from 62 winter to summer (Kausel et al, 1999). 63During embryogenesis, various other transcription factors were shown to be involved 64 in morphogenesis of the primordial pituitary and in specification and differentiation of 65 the specific cell types in mammals (Zhu et al, 2007). In zebrafish similar functions 66 are played by pit1 (Herzog et al, 2003;Nica et al, 2004), eya1 (Lopez et al, 2006; 67 Nica et al, 2006) or asc1 (Pogoda et al, 2006), suggesting a good conservation of 68 the regulation of pituitary ontogenesis from fish to man (Pogoda and 69…”