FGF8 coordinates tissue elongation and cell epithelialization during early kidney tubulogenesis.

Yuji Atsuta,Yoshiko Takahashi

doi:10.1242/dev.122408

Yuji Atsuta, Yoshiko Takahashi

Open Access

https://doi.org/10.1242/dev.122408

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Abstract

When a tubular structure forms during early embryogenesis, tubular elongation and lumen formation (epithelialization) proceed simultaneously in a spatiotemporally coordinated manner. We here demonstrate, using the Wolffian duct (WD) of early chicken embryos, that this coordination is regulated by the expression of FGF8, which shifts posteriorly during body axis elongation. FGF8 acts as a chemoattractant on the leader cells of the elongating WD and prevents them from epithelialization, whereas static (‘rear’) cells that receive progressively less FGF8 undergo epithelialization to form a lumen. Thus, FGF8 acts as a binary switch that distinguishes tubular elongation from lumen formation. The posteriorly shifting FGF8 is also known to regulate somite segmentation, suggesting that multiple types of tissue morphogenesis are coordinately regulated by macroscopic changes in body growth.

Highlights

In many organs, tubular epithelia perform key physiological functions
We asked three questions: (1) what regulates the behavior of leader cells; (2) what determines the relative locations of the leader and static rear cells; and (3) what triggers epithelialization/lumenization? We found that FGF8, which is produced in a caudal region of the embryo (Dubrulle and Pourquie, 2004), plays crucial roles in these processes
By exploiting the simple structure of the Wolffian duct (WD) and the amenability of tissue manipulations in chicken embryos, we have demonstrated that the WD is formed through a remarkably coordinated morphogenesis of tubule elongation and cell epithelialization

Summary

Introduction

They convey food in the gut, exocrine factors from the pancreas and wastes from the kidney. For these functions, tubular integrity is important because its failure would cause pathological defects (Andrew and Ewald, 2010). Tubule formation involves two major, coordinated steps: tubular elongation, a process that controls the length of the tubule; and cell epithelialization, a process that forms an internal lumen. These two events must take place in a spatiotemporally coordinated manner.

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