Retinoic Acid Regulation of Cdx1: an Indirect Mechanism for Retinoids and Vertebral Specification

ABSTRACT Retinoic acid (RA) is required for diverse developmental programs, including vertebral specification. Both RA receptor disruption and excess RA result in homeotic transformations of the axial skeleton. These effects are believed to occur through altered expression ofHox genes, several of which have been demonstrated to be direct RA targets. Members of the cdx (caudal) homeobox gene family are also implicated in regulating Hoxexpression. Disruption of cdx1 results in vertebral homeotic transformations and alteration of Hox expression boundaries; similar homeosis is also observed in cdx2heterozygotes. In Xenopus, gain or loss of Cdx function affects vertebral morphogenesis through a mechanism that also correlates with altered Hox expression. Taken together with the finding of putative Cdx binding motifs in several Hoxpromoters, these data strongly support a role for Cdx members in direct regulation of expression of at least some Hox genes. Most retinoid-responsive Hox genes have not been demonstrated to be direct RA targets, suggesting that intermediaries are involved. Based on these findings, we hypothesized that one or morecdx members may transduce the effects of RA onHox transcription. Consistent with this, we present evidence that cdx1 is a direct RA target gene, suggesting an additional pathway for retinoid-dependent vertebral specification.

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FgHtf1 Regulates Global Gene Expression towards Aerial Mycelium and Conidiophore Formation in the Cereal Fungal Pathogen Fusarium graminearum

Applied and Environmental Microbiology ◽

10.1128/aem.03024-19 ◽

2020 ◽

Vol 86 (9) ◽

Author(s):

Gaili Fan ◽

Huawei Zheng ◽

Kai Zhang ◽

Veena Devi Ganeshan ◽

Stephen Obol Opiyo ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Gene Family ◽

Fusarium Graminearum ◽

Target Genes ◽

Homeobox Gene ◽

Global Gene Expression ◽

Binding Motifs ◽

Content Type ◽

Aerial Growth

ABSTRACT The homeobox gene family of transcription factors (HTF) controls many developmental pathways and physiological processes in eukaryotes. We previously showed that a conserved HTF in the plant-pathogenic fungus Fusarium graminearum, Htf1 (FgHtf1), regulates conidium morphology in that organism. This study investigated the mechanism of FgHtf1-mediated regulation and identified putative FgHtf1 target genes by a chromatin immunoprecipitation assay combined with parallel DNA sequencing (ChIP-seq) and RNA sequencing. A total of 186 potential binding peaks, including 142 genes directly regulated by FgHtf1, were identified. Subsequent motif prediction analysis identified two DNA-binding motifs, TAAT and CTTGT. Among the FgHtf1 target genes were FgHTF1 itself and several important conidiation-related genes (e.g., FgCON7), the chitin synthase pathway genes, and the aurofusarin biosynthetic pathway genes. In addition, FgHtf1 may regulate the cAMP-protein kinase A (PKA)-Msn2/4 and Ca2+-calcineurin-Crz1 pathways. Taken together, these results suggest that, in addition to autoregulation, FgHtf1 also controls global gene expression and promotes a shift to aerial growth and conidiation in F. graminearum by activation of FgCON7 or other conidiation-related genes. IMPORTANCE The homeobox gene family of transcription factors is known to be involved in the development and conidiation of filamentous fungi. However, the regulatory mechanisms and downstream targets of homeobox genes remain unclear. FgHtf1 is a homeobox transcription factor that is required for phialide development and conidiogenesis in the plant pathogen F. graminearum. In this study, we identified FgHtf1-controlled target genes and binding motifs. We found that, besides autoregulation, FgHtf1 also controls global gene expression and promotes conidiation in F. graminearum by activation of genes necessary for aerial growth, FgCON7, and other conidiation-related genes.

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Ldb1, in conjunction with transcriptional regulators of the LIM-homeobox gene family, orchestrates limb patterning and outgrowth during mouse embryonic development

Developmental Biology ◽

10.1016/j.ydbio.2007.03.238 ◽

2007 ◽

Vol 306 (1) ◽

pp. 357-358

Author(s):

Heiner Westphal ◽

Itai Tzchori ◽

Timothy F. Day ◽

Peter J. Carolan ◽

Yangu Zhao ◽

...

Keyword(s):

Embryonic Development ◽

Gene Family ◽

Homeobox Gene ◽

Transcriptional Regulators ◽

Limb Patterning

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Retinoic acid and chick limb bud development

Development ◽

10.1242/dev.113.supplement_1.113 ◽

1991 ◽

Vol 113 (Supplement_1) ◽

pp. 113-121 ◽

Cited By ~ 4

Author(s):

C. Tickle

Keyword(s):

Retinoic Acid ◽

Target Genes ◽

Homeobox Gene ◽

Experimental System ◽

Shoulder Girdle ◽

Limb Bud ◽

Local Concentration ◽

Anterior Position ◽

Mesenchyme Cells ◽

Vitamin A Derivative

The chick limb bud is a powerful experimental system in which to study pattern formation in vertebrate embryos. Exogenously applied retinoic acid, a vitamin A derivative, can bring about changes in pattern and, on several grounds, is a good candidate for an endogenous morphogen. As such, the local concentration of retinoic acid might provide cells with information about their position in relation to one axis of the limb. Alternatively, retinoic acid may be part of a more complex signalling system. Homeobox genes are possible target genes for regulation by retinoic acid in the limb. In particular, one homeobox gene, XlHbox 1 is expressed locally in the mesenchyme of vertebrate forelimbs and might code for an anterior position. When the pattern of the chick wing is changed by retinoic acid or by grafts of signalling tissue such that anterior cells now form posterior structures, the domain of XlHbox 1 expression expands rather than contracts. The expansion of XlHbox 1 expression correlates with shoulder girdle abnormalities. Retinoic acid application leads to visible changes in bud shape and this allows dissection of the way in which patterning is co-ordinated with morphogenesis. Results of recombination experiments and studies of changes in the apical ridge and proliferation in the mesenchyme suggest the following scheme: retinoic acid is involved in specification of position of mesenchyme cells; this specification determines their local interaction with the ridge that controls ridge morphology; the thickened apical ridge permits local proliferation in the underlying mesenchyme. The recent advances in molecular biology that permit analysis of the expression of various interesting genes in developing limbs hold out the promise that further investigation may soon allow a complete account of the patterning process in one part of the vertebrate embryo.

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Isolation and characterization of a downstream target of Pax6 in the mammalian retinal primordium

Development ◽

10.1242/dev.128.20.3987 ◽

2001 ◽

Vol 128 (20) ◽

pp. 3987-3994 ◽

Cited By ~ 2

Author(s):

Gilbert Bernier ◽

Wolfgang Vukovich ◽

Lorenz Neidhardt ◽

Bernhard G. Herrmann ◽

Peter Gruss

Keyword(s):

Transcription Factor ◽

Expression Pattern ◽

Large Scale ◽

Ectopic Expression ◽

Signal Transduction Pathway ◽

Homeobox Gene ◽

Optic Vesicle ◽

Altered Expression ◽

Retina Development ◽

Isolation And Characterization

The transcription factor Pax6 is required for eye morphogenesis in humans, mice and insects, and can induce ectopic eye formation in vertebrate and invertebrate organisms. Although the role of Pax6 has intensively been studied, only a limited number of genes have been identified that depend on Pax6 activity for their expression in the mammalian visual system. Using a large-scale in situ hybridization screen approach, we have identified a novel gene expressed in the mouse optic vesicle. This gene, Necab, encodes a putative cytoplasmic Ca2+-binding protein and coincides with Pax6 expression pattern in the neural ectoderm of the optic vesicle and in the forebrain pretectum. Remarkably, Necab expression is absent in both structures in Pax6 mutant embryos. By contrast, the optic vesicle-expressed homeobox genes Rx, Six3, Otx2 and Lhx2 do not exhibit an altered expression pattern. Using gain-of-function experiments, we show that Pax6 can induce ectopic expression of Necab, suggesting that Necab is a direct or indirect transcriptional target of Pax6. In addition, we have found that Necab misexpression can induce ectopic expression of the homeobox gene Chx10, a transcription factor implicated in retina development. Taken together, our results provide evidence that Necab is genetically downstream of Pax6 and that it is a part of a signal transduction pathway in retina development.

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Uncx4.1 is required for the formation of the pedicles and proximal ribs and acts upstream of Pax9

Development ◽

10.1242/dev.127.11.2251 ◽

2000 ◽

Vol 127 (11) ◽

pp. 2251-2258 ◽

Cited By ~ 1

Author(s):

A. Mansouri ◽

A.K. Voss ◽

T. Thomas ◽

Y. Yokota ◽

P. Gruss

Keyword(s):

Cell Adhesion ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Homeobox Gene ◽

Axial Skeleton ◽

Adhesion Properties ◽

Marker Analysis ◽

Targeted Mutation ◽

Differential Cell

The expression of the homeobox gene Uncx4.1 in the somite is restricted to the caudal half of the newly formed somite and sclerotome. Here we show that mice with a targeted mutation of the Uncx4.1 gene exhibit defects in the axial skeleton and ribs. In the absence of Uncx4.1, pedicles of the neural arches and proximal ribs are not formed. In addition, dorsal root ganglia are disorganized. Histological and marker analysis revealed that Uncx4.1 is not necessary for somite segmentation. It is required to maintain the condensation of the caudal half-sclerotome, from which the missing skeletal elements are derived. The loss of proximal ribs in Pax1/Pax9 double mutants and the data presented here argue for a role of Uncx4.1 upstream of Pax9 in the caudolateral sclerotome. Our results further indicate that Uncx4.1 may be involved in the differential cell adhesion properties of the somite.

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The paired homeobox gene Uncx4.1 specifies pedicles, transverse processes and proximal ribs of the vertebral column

Development ◽

10.1242/dev.127.11.2259 ◽

2000 ◽

Vol 127 (11) ◽

pp. 2259-2267 ◽

Cited By ~ 4

Author(s):

M. Leitges ◽

L. Neidhardt ◽

B. Haenig ◽

B.G. Herrmann ◽

A. Kispert

Keyword(s):

Transcription Factor ◽

Vertebral Column ◽

Cell Mass ◽

Homeobox Gene ◽

Mesenchymal Cell ◽

Axial Skeleton ◽

Intervertebral Discs ◽

Medial Part ◽

Targeted Mutation ◽

Vertebral Bodies

The axial skeleton develops from the sclerotome, a mesenchymal cell mass derived from the ventral halves of the somites, segmentally repeated units located on either side of the neural tube. Cells from the medial part of the sclerotome form the axial perichondral tube, which gives rise to vertebral bodies and intervertebral discs; the lateral regions of the sclerotome will form the vertebral arches and ribs. Mesenchymal sclerotome cells condense and differentiate into chondrocytes to form a cartilaginous pre-skeleton that is later replaced by bone tissue. Uncx4.1 is a paired type homeodomain transcription factor expressed in a dynamic pattern in the somite and sclerotome. Here we show that mice homozygous for a targeted mutation of the Uncx4.1 gene die perinatally and exhibit severe malformations of the axial skeleton. Pedicles, transverse processes and proximal ribs, elements derived from the lateral sclerotome, are lacking along the entire length of the vertebral column. The mesenchymal anlagen for these elements are formed initially, but condensation and chondrogenesis do not occur. Hence, Uncx4.1 is required for the maintenance and differentiation of particular elements of the axial skeleton.

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Identifying targets of the rough homeobox gene of Drosophila: evidence that rhomboid functions in eye development

Development ◽

10.1242/dev.116.2.335 ◽

1992 ◽

Vol 116 (2) ◽

pp. 335-346 ◽

Cited By ~ 26

Author(s):

M. Freeman ◽

B.E. Kimmel ◽

G.M. Rubin

Keyword(s):

Cell Fate ◽

Target Genes ◽

Eye Development ◽

Expression Patterns ◽

Ectopic Expression ◽

Homeobox Gene ◽

Homeodomain Protein ◽

Dorsoventral Patterning ◽

Altered Expression ◽

Enhancer Trap Lines

In order to identify potential target genes of the rough homeodomain protein, which is known to specify some aspects of the R2/R5 photoreceptor subtype in the Drosophila eye, we have carried out a search for enhancer trap lines whose expression is rough-dependent. We crossed 101 enhancer traps that are expressed in the developing eye into a rough mutant background, and have identified seven lines that have altered expression patterns. One of these putative rough target genes is rhomboid, a gene known to be required for dorsoventral patterning and development of some of the nervous system in the embryo. We have examined the role of rhomboid in eye development and find that, while mutant clones have only a subtle phenotype, ectopic expression of the gene causes the non-neuronal mystery cells to be transformed into photoreceptors. We propose that rhomboid is a part of a partially redundant network of genes that specify photoreceptor cell fate.

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Expression of the LIM class homeobox gene Xlim-1 in pronephros and CNS cell lineages of Xenopus embryos is affected by retinoic acid and exogastrulation

Development ◽

10.1242/dev.120.6.1525 ◽

1994 ◽

Vol 120 (6) ◽

pp. 1525-1536 ◽

Cited By ~ 8

Author(s):

M. Taira ◽

H. Otani ◽

M. Jamrich ◽

I.B. Dawid

Keyword(s):

Retinoic Acid ◽

Organizer Region ◽

Homeobox Gene ◽

Second Phase ◽

Cell Specification ◽

Spemann Organizer ◽

Xenopus Embryos ◽

Prechordal Mesoderm ◽

The Central Nervous System ◽

Lateral Mesoderm

The LIM class homeobox gene Xlim-1 is expressed in Xenopus embryos in the lineages leading to (i) the notochord, (ii) the pronephros, and (iii) certain cells of the central nervous system (CNS). In its first expression phase, Xlim-1 mRNA arises in the Spemann organizer region, accumulates in prechordal mesoderm and notochord during gastrulation, and decays in these tissues during neurula stages except that it persists in the posterior tip of the notochord. In the second phase, expression in lateral mesoderm begins at late gastrula, and converges to the pronephros at tailbud stages. Expression in a central location of the neural plate also initiates at late gastrula, expands anteriorly and posteriorly, and becomes established in the lateral regions of the spinal cord and hindbrain at tailbud stages. Thus Xlim-1 expression precedes morphogenesis, suggesting that it may be involved in cell specification in these lineages. Enhancement of Xlim-1 expression by retinoic acid (RA) was first detectable in the dorsal mesoderm at initial gastrula. During gastrulation and early neurulation, RA strongly enhanced Xlim-1 expression in all three lineages and also expanded its expressing domains; this overexpression correlated well with RA phenotypes such as enlarged pronephros and hindbrain-like structure. Exogastrulation reduced Xlim-1 expression in the lateral mesoderm and ectoderm but not in the notochord, suggesting that the second phase of Xlim-1 expression requires mesoderm/ectoderm interactions. RA treatment of exogastrulae did not revert this reduction.

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