A Charboneau

A Ciau-Uitz

A Cvejic

A Mamo

AC Brun

AJ Davidson

AJ Durston

AJ Waskiewicz

Aseervatham Anusha Amali

AT Chen

B Argiropoulos

C Abramovich

C Nolte

C Thisse

C Winkler

CB Kimmel

CB Moens

Christoph Winkler

D Traver

E Eklund

E Ellertsdottir

EJ Paik

F Liu

GG Wang

GS Horan

J Deschamps

JF DiMartino

JM Bjornsson

JW Xiong

K Kissa

K Minehata

K Shanmugam

K Stankunas

KH Ko

KM Vogeli

Lawrence Sie

LM Pillay

M Iacovino

M Kmita

M Magnusson

Mark Featherstone

ND Lawson

P Di Rosa

P diIorio

P Wong

R Ramírez-Solis

RM Warga

RS Mann

S Hoegg

S Isogai

SA Wacker

SB Bahrami

SJ Gaunt

Stephane Germain

T Hisa

T Iimura

T Peterkin

TE North

V Azcoitia

VE Prince

X Wan

Z Wang

PLoS ONE

PubMed

Amali Aseervatham Anusha

Sie Lawrence

Winkler Christoph

Featherstone Mark

Public Library of Science (PLOS)

 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

Mice lacking the 4th-group paralog Hoxd4 display malformations of the anterior vertebral column, but are viable and fertile. Here, we report that zebrafish embryos having decreased function of the orthologous hoxd4a gene manifest striking perturbations in vasculogenesis, angiogenesis and primitive and definitive hematopoiesis. These defects are preceded by reduced expression of the hemangioblast markers scl1, lmo2 and fli1 within the posterior lateral plate mesoderm (PLM) at 13 hours post fertilization (hpf). Epistasis analysis revealed that hoxd4a acts upstream of meis1.1 but downstream of cdx4 as early as the shield stage in ventral-most mesoderm fated to give rise to hemangioblasts, leading us to propose that loss of hoxd4a function disrupts hemangioblast specification. These findings place hoxd4a high in a genetic hierarchy directing hemangioblast formation downstream of cdx1/cdx4 and upstream of meis1.1. An additional consequence of impaired hoxd4a and meis1.1 expression is the deregulation of multiple Hox genes implicated in vasculogenesis and hematopoiesis which may further contribute to the defects described here. Our results add to evidence implicating key roles for Hox genes in their initial phase of expression early in gastrulation

Directory of Open Access Journals

Zebrafish hoxd4a acts upstream of meis1.1 to direct vasculogenesis, angiogenesis and hematopoiesis.

Mice lacking the 4th-group paralog Hoxd4 display malformations of the anterior vertebral column, but are viable and fertile.
Here, we report that zebrafish embryos having decreased function of the orthologous hoxd4a gene manifest striking
perturbations in vasculogenesis, angiogenesis and primitive and definitive hematopoiesis. These defects are preceded by
reduced expression of the hemangioblast markers scl1, lmo2 and fli1 within the posterior lateral plate mesoderm (PLM) at 13
hours post fertilization (hpf). Epistasis analysis revealed that hoxd4a acts upstream of meis1.1 but downstream of cdx4 as
early as the shield stage in ventral-most mesoderm fated to give rise to hemangioblasts, leading us to propose that loss of
hoxd4a function disrupts hemangioblast specification. These findings place hoxd4a high in a genetic hierarchy directing
hemangioblast formation downstream of cdx1/cdx4 and upstream of meis1.1. An additional consequence of impaired
hoxd4a and meis1.1 expression is the deregulation of multiple Hox genes implicated in vasculogenesis and hematopoiesis
which may further contribute to the defects described here. Our results add to evidence implicating key roles for Hox genes
in their initial phase of expression early in gastrulation.Published versio

Amali, Aseervatham Anusha

Sie, Lawrence

Winkler, Christoph

Featherstone, Mark

DR-NTU (Digital Repository of NTU)

Zebrafish hoxd4a acts upstream of meis1.1 to direct vasculogenesis, angiogenesis and hematopoiesis

<div>Mice lacking the 4th-group paralog Hoxd4 display malformations of the anterior vertebral column, but are viable and fertile. Here, we report that zebrafish embryos having decreased function of the orthologous hoxd4a gene manifest striking perturbations in vasculogenesis, angiogenesis and primitive and definitive hematopoiesis. These defects are preceded by reduced expression of the hemangioblast markers scl1, lmo2 and fli1 within the posterior lateral plate mesoderm (PLM) at 13 hours post fertilization (hpf). Epistasis analysis revealed that hoxd4a acts upstream of meis1.1 but downstream of cdx4 as early as the shield stage in ventral-most mesoderm fated to give rise to hemangioblasts, leading us to propose that loss of hoxd4a function disrupts hemangioblast specification. These findings place hoxd4a high in a genetic hierarchy directing hemangioblast formation downstream of cdx1/cdx4 and upstream of meis1.1. An additional consequence of impaired hoxd4a and meis1.1 expression is the deregulation of multiple Hox genes implicated in vasculogenesis and hematopoiesis which may further contribute to the defects described here. Our results add to evidence implicating key roles for Hox genes in their initial phase of expression early in gastrulation.</div

Aseervatham Anusha Amali (390160)

Lawrence Sie (390161)

Christoph Winkler (80764)

Mark Featherstone (342902)

The Francis Crick Institute

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

Crossref

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

Digital Repository - Nanyang Technological University

http://dx.doi.org/10.1371/journal.pone.0058857

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

Abstract

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Public Library of Science (PLOS)

Directory of Open Access Journals

DR-NTU (Digital Repository of NTU)

The Francis Crick Institute

Crossref

Digital Repository - Nanyang Technological University