Retinoic acid is a key regulatory switch determining the difference between lung and thyroid fates in Xenopus laevis

Jean H Wang,Fred Possmayer,Steven J Deimling,Nicole E D'Alessandro,Lin Zhao,Thomas A Drysdale

doi:10.1186/1471-213x-11-75

Jean H Wang, Fred Possmayer + Show 4 more

Open Access

https://doi.org/10.1186/1471-213x-11-75

Copy DOI

Abstract

BackgroundThe lung and thyroid are derived from the anterior endoderm. Retinoic acid and Fgf signalling are known to be essential for development of the lung in mouse but little is known on how the lung and thyroid are specified in Xenopus.ResultsIf either retinoic acid or Fgf signalling is inhibited, there is no differentiation of the lung as assayed by expression of sftpb. There is no change in expression of thyroid gland markers when retinoic acid signalling is blocked after gastrulation and when Fgf signalling is inhibited there is a short window of time where pax2 expression is inhibited but expression of other markers is unaffected. If exogenous retinoic acid is given to the embryo between embryonic stages 20 and 26, the presumptive thyroid expresses sftpb and sftpc, specific markers of lung differentiation and expression of key thyroid transcription factors is lost. When the presumptive thyroid is transplanted into the posterior embryo, it also expresses sftpb, although pax2 expression is not blocked.ConclusionsAfter gastrulation, retinoic acid is required for lung but not thyroid differentiation in Xenopus while Fgf signalling is needed for lung but only for early expression of pax2 in the thyroid. Exposure to retinoic acid can cause the presumptive thyroid to switch to a lung developmental program.

Highlights

The lung and thyroid are derived from the anterior endoderm
We demonstrate that the requirement for retinoic acid (RA) and fibroblast growth factor (Fgf) signalling in lung differentiation is conserved in Xenopus
At stage 34, expression of nkx2.1 was detectable in the forming lung. The expression of these key transcription factors preceded the expression of the lung differentiation markers sftpb and sftpc both of which were detectable at stage 38

Summary

Introduction

The lung and thyroid are derived from the anterior endoderm. Retinoic acid and Fgf signalling are known to be essential for development of the lung in mouse but little is known on how the lung and thyroid are specified in Xenopus. Specific transcription factors are associated with each of these organ systems in later development, expression of key transcription factors at early stages is Recently, in addition to Fgf signalling, it has been demonstrated that graded levels of retinoic acid (RA) are important in chick for defining the different regions along the anterior-posterior axis of the developing endoderm [13]. There are discrete regions of expression in the head but on the ventral side, there is little expression anterior to the forming heart [18,19] This would predict that the forming lung should be exposed to RA but that more posterior endoderm would be exposed to lower levels of RA. Expression of aldh1a2 is found in specific gut regions where it is required for the gut looping process [20]

Objectives

Methods

Results

Discussion

Conclusion