UNSW Embryology

Endocrine Molecular Development

© Dr Mark Hill (2011)

Acknowledgements

Introduction

This section of notes under development. Currently only some reference materials are listed.

• Follicular cells of the thyroid gland require Pax8 gene function. Mansouri A, Chowdhury K, Gruss P Nat Genet 1998 May;19(1):87-90
  • The thyroid gland develops from two distinct embryonic lineages: follicular cells (which produce thyroxine) and parafollicular C-cells (which produce calcitonin) are of endodermal and neural crest origin, respectively. Little is known about the molecular mechanisms governing the generation of these different cell types. Mice lacking the transcription factor Ttf1 lack both cell types and thus are unable to develop a thyroid gland. By analysis of Pax8-/- mice, we demonstrate that Pax8 is required for the formation of the follicular cells in the thyroid. We present evidence that Pax8 is necessary for providing cues for the differentiation of competent endoderm primordia into thyroxin-producing follicular cells.
• TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation. Zannini M, Avantaggiato V, Biffali E, Arnone MI, Sato K, Pischetola M, Taylor BA, Phillips SJ, Simeone A, Di Lauro R EMBO J 1997 Jun 2;16(11):3185-97
  • Expression of thyroglobulin (Tg) and thyroperoxidase (TPO) genes in thyroid follicular cells occurs in the mouse at embryonic day (E)14.5. Two transcription factors, TTF-1 and Pax-8, have been implicated in transcriptional activation of Tg and TPO, even though the onset of their expression is at E9.5, suggesting that additional events are necessary for transcriptional activation of Tg and TPO genes. We report in this paper the cloning of TTF-2, a DNA binding protein that recognizes sites on both Tg and TPO promoters. TTF-2 is a new forkhead domain-containing protein whose expression is restricted to the endodermal lining of the foregut and to the ectoderm that will give rise to the anterior pituitary. TTF-2 shows transient expression in the developing thyroid and anterior pituitary. In the thyroid, TTF-2 expression is down-regulated just before the onset of Tg and TPO gene expression, suggesting that this transcription factor plays the role in development of a negative controller of thyroid-specific gene expression.
• A model for the development of the hypothalamic-pituitary axis: transcribing the hypophysis. Kioussi C, Carriere C, Rosenfeld MG Mech Dev 1999 Mar;81(1-2):23-35 [PubMed]
  • Mammalian organogenesis involves a sequential program to generate cells with specific fates and phenotypes from a common primordium, which is hypothesized to be the consequence of regulated overlapping patterns of expression of specific sets of transcription factors in a precise spatiotemporal manner. The hypothalamic-pituitary axis is critical for survival and homeostasis, controlling growth, reproduction, metabolism and behavior, and constitutes an ideal model in which to define the molecular markers to emergence of specific cell phenotypes from a common primordium. Development of the anterior pituitary gland is controlled by sequential series of gradients of specific signaling molecules that, in turn, appear to coordinate the expression of specific combinations of transcription factor-encoding genes, many of which as tissue-specific or tissue restricted factors that serially dictate cell-type determination and terminal differentiation events that underlie the differentiated cell phenotype.

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