A branching morphogenesis program governs embryonic growth of the thyroid gland

Liang S,Barila G,Nilsson M,Johansson E,Fagman H,Altschuler Dl

doi:10.1530/ey.15.3.2

Abstract

The developmental program that regulates thyroid progenitor cell proliferation is largely unknown. Here, we show that branching-like morphogenesis is a driving force to attain final size of the embryonic thyroid gland in mice. Sox9, a key factor in branching organ development, distinguishes Nkx2-1+ cells in the thyroid bud from the progenitors that originally form the thyroid placode in anterior endoderm. As lobes develop the thyroid primordial tissue branches several generations. Sox9 and Fgfr2b are co-expressed distally in the branching epithelium prior to folliculogenesis. The thyroid in Fgf10 null mutants has a normal shape but is severely hypoplastic. Absence of Fgf10 leads to defective branching and disorganized angiofollicular units although Sox9/Fgfr2b expression and the ability of cells to differentiate and form nascent follicles are not impaired. These findings demonstrate a novel mechanism of thyroid development reminiscent of the Fgf10-Sox9 program that characterizes organogenesis in classical branching organs, and provide clues to aid understanding of how the endocrine thyroid gland once evolved from an exocrine ancestor present in the invertebrate endostyle.

Highlights

Mouse thyroid morphogenesis recapitulates in less than one week the developmental program of the human thyroid gland (Nilsson and Fagman, 2017)
Sox9 identifies a subset of proliferating thyroid progenitors Because Sox9 regulates branching morphogenesis by preserving a pool of undifferentiated and growth-prone progenitors in the lung (Chang et al, 2013; Rockich et al, 2013) and exocrine glands (Seymour et al, 2012; Chen et al, 2014; Chatzeli et al, 2017), we investigated the possibility that it has a similar role in thyroid development by first monitoring the distribution of Ki-67 (Mki67)expressing cells during branching growth of the embryonic thyroid
The present study identifies a novel mechanism of growth specific to branching morphogenesis in the embryonic thyroid in mice

Summary

Introduction

Mouse thyroid morphogenesis recapitulates in less than one week the developmental program of the human thyroid gland (Nilsson and Fagman, 2017). Bud enlargement is not accomplished by localized proliferation indicating that embryonic thyroid growth at this developmental stage is achieved by annexing cells from adjacent endoderm (Kinebrew and Hilfer, 2001; Fagman et al, 2006). It is not until the detached thyroid primordium migrates downwards that progenitor cells are triggered to multiply intensely leading to the prospective gland, after finishing migration, bifurcating and growing bilaterally (Fagman et al, 2006); this represents the starting point of the bilobation process. Molecular mechanisms that govern primordial growth of the embryonic thyroid beyond the bud stage are poorly understood (Nilsson and Fagman, 2017)

Methods

Results

Conclusion