Hand2 inhibits kidney specification while promoting vein formation within the posterior mesoderm.

Elliot A Perens,Deborah Yelon,Zayra V Garavito-Aguilar,Gina P Guio-Vega,Yocheved L Schindler,Karen T Peña

doi:10.7554/elife.19941

Elliot A Perens, Deborah Yelon + Show 4 more

Open Access

https://doi.org/10.7554/elife.19941

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Abstract

Proper organogenesis depends upon defining the precise dimensions of organ progenitor territories. Kidney progenitors originate within the intermediate mesoderm (IM), but the pathways that set the boundaries of the IM are poorly understood. Here, we show that the bHLH transcription factor Hand2 limits the size of the embryonic kidney by restricting IM dimensions. The IM is expanded in zebrafish hand2 mutants and is diminished when hand2 is overexpressed. Within the posterior mesoderm, hand2 is expressed laterally adjacent to the IM. Venous progenitors arise between these two territories, and hand2 promotes venous development while inhibiting IM formation at this interface. Furthermore, hand2 and the co-expressed zinc-finger transcription factor osr1 have functionally antagonistic influences on kidney development. Together, our data suggest that hand2 functions in opposition to osr1 to balance the formation of kidney and vein progenitors by regulating cell fate decisions at the lateral boundary of the IM.

Highlights

Organs arise from precisely defined territories containing progenitor cells with specific developmental potential
Kidney progenitor cells originate from the intermediate mesoderm (IM), a pair of narrow bilateral stripes within the posterior mesoderm, flanked by the lateral plate mesoderm (LPM) that gives rise to vessels and by the paraxial mesoderm that gives rise to bone, cartilage, and skeletal muscle
Hand2 is expressed in the posterior mesoderm (Angelo et al, 2000; Fernandez-Teran et al, 2000; Srivastava et al, 1997; Thomas et al, 1998; Yelon et al, 2000; Yin et al, 2010), its influence on patterning this tissue has not been extensively explored. Through both loss2 of-function and gain-of-function studies, we find that hand2 limits the size of the kidney 3 by repressing IM formation while promoting venous progenitor formation. hand2 is 4 expressed laterally adjacent to the IM, and a set of venous progenitors arise at the 5 interface between the hand2-expressing cells and the IM

Summary

INTRODUCTION

Organs arise from precisely defined territories containing progenitor cells with specific developmental potential. Hand is expressed in the posterior mesoderm (Angelo et al, 2000; Fernandez-Teran et al., 2000; Srivastava et al, 1997; Thomas et al, 1998; Yelon et al, 2000; Yin et al, 2010), its influence on patterning this tissue has not been extensively explored Through both loss of-function and gain-of-function studies, we find that hand limits the size of the kidney 3 by repressing IM formation while promoting venous progenitor formation. Our data demonstrate a novel mechanism for defining territory boundaries within the posterior mesoderm: hand represses IM formation to establish its lateral boundary while promoting venous progenitor formation in this region These important functions of Hand help to define the precise dimensions and components of the kidneys and vasculature. These findings have implications for understanding the genetic basis of congenital anomalies of the kidney and urinary tract (CAKUT) and for developing new approaches in regenerative medicine

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MATERIALS AND METHODS