A gene regulatory network anchored by LIM homeobox 1 for embryonic head development

TY - JOUR

T1 - A gene regulatory network anchored by LIM homeobox 1 for embryonic head development

AU - Sibbritt, Tennille

AU - Ip, Chi K.

AU - Khoo, Poh Lynn

AU - Wilkie, Emilie

AU - Jones, Vanessa

AU - Sun, Jane Q.J.

AU - Shen, Joanne X.

AU - Peng, Guangdun

AU - Han, Jing Dong J.

AU - Jing, Naihe

AU - Osteil, Pierre

AU - Ramialison, Mirana

AU - Tam, Patrick P.L.

AU - Fossat, Nicolas

PY - 2018

Y1 - 2018

N2 - Development of the embryonic head is driven by the activity of gene regulatory networks of transcription factors. LHX1 is a homeobox transcription factor that plays an essential role in the formation of the embryonic head. The loss of LHX1 function results in anterior truncation of the embryo caused by the disruption of morphogenetic movement of tissue precursors and the dysregulation of WNT signaling activity. Profiling the gene expression pattern in the Lhx1 mutant embryo revealed that tissues in anterior germ layers acquire posterior tissue characteristics, suggesting LHX1 activity is required for the allocation and patterning of head precursor tissues. Here, we used LHX1 as an entry point to delineate its transcriptional targets and interactors and construct a LHX1-anchored gene regulatory network. Using a gain-of-function approach, we identified genes that immediately respond to Lhx1 activation. Meta-analysis of the datasets of LHX1-responsive genes and genes expressed in the anterior tissues of mouse embryos at head-fold stage, in conjunction with published Xenopus embryonic LHX1 (Xlim1) ChIP-seq data, has pinpointed the putative transcriptional targets of LHX1 and an array of genetic determinants functioning together in the formation of the mouse embryonic head.

AB - Development of the embryonic head is driven by the activity of gene regulatory networks of transcription factors. LHX1 is a homeobox transcription factor that plays an essential role in the formation of the embryonic head. The loss of LHX1 function results in anterior truncation of the embryo caused by the disruption of morphogenetic movement of tissue precursors and the dysregulation of WNT signaling activity. Profiling the gene expression pattern in the Lhx1 mutant embryo revealed that tissues in anterior germ layers acquire posterior tissue characteristics, suggesting LHX1 activity is required for the allocation and patterning of head precursor tissues. Here, we used LHX1 as an entry point to delineate its transcriptional targets and interactors and construct a LHX1-anchored gene regulatory network. Using a gain-of-function approach, we identified genes that immediately respond to Lhx1 activation. Meta-analysis of the datasets of LHX1-responsive genes and genes expressed in the anterior tissues of mouse embryos at head-fold stage, in conjunction with published Xenopus embryonic LHX1 (Xlim1) ChIP-seq data, has pinpointed the putative transcriptional targets of LHX1 and an array of genetic determinants functioning together in the formation of the mouse embryonic head.

KW - gene regulatory network

KW - Lhx1

KW - mouse

KW - WNT signaling

U2 - 10.1002/dvg.23246

DO - 10.1002/dvg.23246

M3 - Journal article

C2 - 30114334

AN - SCOPUS:85053481724

SN - 1526-954X

VL - 56

JO - Genesis

JF - Genesis

IS - 9

M1 - e23246

ER -