Invited article
Molecular genetics of pituitary development in zebrafish

https://doi.org/10.1016/j.semcdb.2007.04.004Get rights and content

Abstract

The pituitary gland of vertebrates consists of two major parts, the neurohypophysis (NH) and the adenohypophysis (AH). As a central part of the hypothalamo-hypophyseal system (HHS), it constitutes a functional link between the nervous and the endocrine system to regulate basic body functions, such as growth, metabolism and reproduction. The development of the AH has been intensively studied in mouse, serving as a model for organogenesis and differential cell specification. However, given that the AH is a relatively recent evolutionary advance of the chordate phylum, it is also interesting to understand its development in lower chordate systems. In recent years, the zebrafish has emerged as a powerful lower vertebrate system for developmental studies, being amenable for large-scale genetic approaches, embryological manipulations, and in vivo imaging.

Here, we present an overview of current knowledge of the mechanisms and genetic control of pituitary formation during zebrafish development. First, we describe the components of the zebrafish HHS, and the different pituitary cell types and hormones, followed by a description of the different steps of normal pituitary development. The central part of the review deals with the genes found to be essential for zebrafish AH development, accompanied by a description of the corresponding mutant phenotypes. Finally, we discuss future directions, with particular focus on evolutionary aspects, and some novel functional aspects with growing medical and social relevance.

Section snippets

The zebrafish as a powerful system for genetics, functional genomics, and in vivo imaging

Why study pituitary development in the tropical fresh water fish and aquarium pet Danio rerio, commonly called zebrafish, while a lot is already known about the molecular and genetic control of pituitary formation in the prime mammalian model system, the mouse [1], [2]?

First, there is an evolutionary aspect. Although a recent report describes a potential functional equivalent in the fruitfly Drosophila melanogaster [3], it is commonly believed that the pituitary gland as a central component of

The hypothalamo-hypophyseal system

Similar to its position in mammals, the pituitary gland or hypophysis of adult zebrafish is located in a bony hollow beneath the hypothalamus, just posterior to the optic chiasm (Fig. 1E and F). At larval stages, it is positioned directly above the fenestra of the neurocranial cartilage, separated from the underlying oral cavity epithelium by a layer of collagen fibrils (Fig. 1C) [13]. As a central part of the HHS, the pituitary links the nervous and the endocrine systems to regulate an array

Development of the zebrafish adenohypophysis

From the developmental biologist's point of view, the AH constitutes an extremely useful model to study the principles of organogenesis and differential cell specification, since it consists of a well defined and spatially arranged set of different cell types that develop from a common pool of precursor cells. In all vertebrates, such AH precursor cells can be traced back to early neural plate stages when neural and presumptive epidermal ectoderm are separated by the pre-placodal ectoderm (PPE)

The zebrafish pituitary mutants & morphants

Reverse genetics and transgenesis-based overexpression studies have provided crucial insights into the molecular network regulating pituitary development in the mouse. Obtained data have led to a model according to which paracrine factors secreted from the ventral diencephalon – namely Wnt5a, the bone morphogenetic protein Bmp4, and the fibroblast growth factors Fgf8 and Fgf10 – induce a domain within the stomodeal ectoderm to form the AH primordium. After the primordium has progressed into

Conclusions and perspectives

Altogether, 12 genes essential for various steps of zebrafish AH development have been identified thus far, six of which encode components of the hedgehog signaling pathway (see Table 1). Clearly, this is only a small fraction of the entire genetic control system, and many questions remain open. The conducted genetic screens have been far from saturation, as underlined by the observation that more and more AH phenotypes are obtained by morpholino knock-downs, while the corresponding mutants are

Acknowledgements

We thank Heinz Schwarz and Agustin Zapata for the photos shown in Fig. 1C and D, respectively, and Marc Muller for communicating unpublished results. HMP and MH were supported by the Max-Planck Society and by SFB 592 of the German Research Foundation (DFG).

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