Neural crest and pituitary development

Heather C. Etchevers1, Christine Vincent and Gérard Couly 2



Running head: Neural crest and pituitary development


Institut d'Embryologie Cellulaire et Moléculaire du CNRS et du Collège de France
49bis avenue de la Belle Gabrielle
94736 Nogent-sur-Marne Cedex
France

and

2Service de Stomatologie
Hôpital Necker - Enfants Malades
149 rue de Sèvres
75015 Paris
France

1To whom correspondence should be sent.

Telephone: (33) 1 45 14 15 15
Fax: (33) 1 48 73 43 77
E-mail: etchever@infobiogen.fr

Introduction
The pituitary gland is composed of three functionally and histologically distinct regions, the
anterior, intermediate and posterior lobes. These arise from two distinct embryonic primordia.
The anterior (adeno-) hypophysis becomes visible in humans at the end of the first month of
development. It develops from an invagination of the ectoderm of the stomodeal roof, called
Rathke’s pouch. The intermediate lobe arises from the dorsal part of Rathke’s pouch closest to
the diencephalon, as has been shown in the fetal rabbit by Schimchowitsch et al. [1]. In
contrast, the posterior (neuro-) hypophysis pinches off of the ventral diencephalon, remaining
attached by a bridge which will develop into the hypophyseal stalk.
Towards the end of the second month, the developing pituitary establishes its links to the
hypothalamus by the progressive elaboration of the hypophyseal stalk, the median eminence
and the venous portal circulations. The architecture of the human hypothalamo-hypophyseal
system is schematized in Figure 1. At the end of embryonic development, the diverse
elements of the pituitary gland are grouped together within the sella turcica of the sphenoid
bone complex. This chapter discusses the origins of the anlagen of the pituitary gland and
their relationship to the embryological cell population, the neural crest.
Fish, amphibian, avian and mammalian animal model systems have all made contributions to
understanding the multiple origins of pituitary components and inductive influences acting
during embryogenesis. Our work has employed the technique of creating quail-chick
chimeras, developed by Le Douarin [2] (reviewed in [3]). Cells from the donor species can be
distinguished from those of the host by a choice of histological or immunocytochemical
techniques. As there is perfect integration of the donor cells within the host, it is possible to
follow their differentiation in any given location and from various time points in
embryogenesis. This technique has been particularly useful in the study of the embryonic cell
population known as the neural crest. Neural crest cells (NCC) delaminate from the boundary
between ectoderm and the neuroepithelial plate as the latter forms a tube which will create the
axis of the central nervous system. They then disperse throughout the body and participate in
the development of a plethora of tissues and organs (Table 1).
Using such quail-chick chimeras, we constructed a map of the presumptive territories
corresponding to the adenohypophysis and neurohypophysis in the open neural plate [4,5].
We also observed that cephalic NCC penetrate into the tissue of the pituitary gland. There
they give rise to interstitial cells and vascular pericytes [4,6]. Surrounding the gland, NCC
also participate in the smooth muscle walls of the hypophyseal arteries and veins, and
compose the bones of the anterior part of the sella turcica [7].

The presumptive adenohypophysis is located in the anterior transverse neural
fold
When determining the location of the presumptive anterior pituitary in the avian neurula, we
examined the derivatives of the anterior neural plate and its surrounding neural folds using
small grafts. The sum of this data is known as a fate map, and the chimeras were constructed
at a stage when the embryos had 3 somite pairs (3ss). Pieces of quail embryos on the order of
0.006 mm2 were grafted into isochronic chicken embryos, after removing the equivalent
regions of the host. Chimeric embryos were sacrificed on embryonic days (E)3, E5, E7 and
E12, and the grafted cells traced.
At E3, after grafting a median piece of the anterior transverse neural fold (Figure 2A, 2B) one
can already see that Rathke’s pouch, the precursor to the adenohypophysis, is of donor origin.