Identification of a Face Enhancer Reveals Direct Regulation of LIM Homeobox 8 (Lhx8) by Wingless-Int (WNT)/β-Catenin Signaling

Malt, André Landin; Cesario, Jeffry M.; Tang, Zuojian; Brown, Stuart M.; Jeong, Juhee

doi:10.1074/jbc.m114.592014

Cited by 13 publications

(9 citation statements)

References 102 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4C). In agreement with reports in mouse embryonic limb and face (Attanasio et al, 2013;Landin Malt et al, 2014), we found that all these regions were enriched for H3K27ac and negative for H3K27me3 chromatin marks, indicating an active and open chromatin state at these sites in midfacial tissues (Fig. 4D) (Creyghton et al, 2010;Cheng et al, 2014;Yue et al, 2014;Long et al, 2016).…”

Section: Presence Of 'Transitional' Cells In the λ Epithelia And Of Csupporting

confidence: 92%

See 1 more Smart Citation

Face morphogenesis is promoted by Pbx-dependent EMT via regulation of Snail1 during frontonasal prominence fusion

Losa

Risolino

et al. 2018

Development

View full text Add to dashboard Cite

Human cleft lip with or without cleft palate (CL/P) is a common craniofacial abnormality caused by impaired fusion of the facial prominences. We have previously reported that, in the mouse embryo, epithelial apoptosis mediates fusion at the seam where the prominences coalesce. Here, we show that apoptosis alone is not sufficient to remove the epithelial layers. We observed morphological changes in the seam epithelia, intermingling of cells of epithelial descent into the mesenchyme and molecular signatures of epithelial-mesenchymal transition (EMT). Utilizing mouse lines with cephalic epithelium-specific Pbx loss exhibiting CL/P, we demonstrate that these cellular behaviors are Pbx dependent, as is the transcriptional regulation of the EMT driver Snail1. Furthermore, in the embryo, the majority of epithelial cells expressing high levels of Snail1 do not undergo apoptosis. Pbx1 loss- and gain-of-function in a tractable epithelial culture system revealed that Pbx1 is both necessary and sufficient for EMT induction. This study establishes that Pbx-dependent EMT programs mediate murine upper lip/primary palate morphogenesis and fusion via regulation of Snail1. Of note, the EMT signatures observed in the embryo are mirrored in the epithelial culture system.

show abstract

Section: Presence Of 'Transitional' Cells In the λ Epithelia And Of Csupporting

confidence: 92%

“…4A). All four elements showed an active chromatin state based on enrichment by p300 and H3K27Ac in mouse embryonic midfaces, as reported elsewhere (Attanasio et al, 2013;Landin Malt et al, 2014;Yue et al, 2014) (Fig. 4A).…”

Section: Presence Of 'Transitional' Cells In the λ Epithelia And Of Csupporting

confidence: 86%

Face morphogenesis is promoted by Pbx-dependent EMT via regulation of Snail1 during frontonasal prominence fusion

Losa

Risolino

et al. 2018

Development

View full text Add to dashboard Cite

show abstract

“…To this end, FGF8b or TGFβ3 signaling pathways and other Lhx8 ‐related pathways may by functionally important in palatogenesis. For example, a gene deficiency in a set such as T‐box genes and wingless‐int ( Wnt ) (81–84) also results in cleft palate. One of the enhancers ( Lhx8 _enh1) located upstream of Lhx8 appears to be a direct target of the Wnt/β‐catenin pathway.…”

Section: Lhx6 and ‐8 In Palatogenesismentioning

confidence: 99%

“…One of the enhancers ( Lhx8 _enh1) located upstream of Lhx8 appears to be a direct target of the Wnt/β‐catenin pathway. This pathway appears to be essential for Lhx8 expression in cells isolated from the maxillary arch (84).…”

Section: Lhx6 and ‐8 In Palatogenesismentioning

confidence: 99%

Lhx6 and Lhx8: cell fate regulators and beyond

et al. 2015

View full text Add to dashboard Cite

As transcription factors of the lines (LIN)-11/Islet (Isl)-1/mitosis entry checkpoint (MEC)-3 (LIM)-homeobox subfamily, LIM homeobox (Lhx)6 and -8 are remarkably conserved and involved in the morphogenesis of multiple organ systems. Lhx6 and -8 play overlapping and distinctive roles, but in general act as cell fate mediators and in turn are regulated by several transcriptional factors, such as sonic hedgehog, fibroblast growth factors, and wingless-int (Wnt)/b-catenin. In this review, we first summarize Lhx6 and -8 distributions in development and then explore how Lhx6 and -8 act as transcription factors and coregulators of cell lineage specification. Known Lhx6 and -8 functions and targets are outlined in neurogenesis, craniofacial development, and germ cell differentiation. The underlying mechanisms of Lhx6 and -8 in regulating cell fate remain elusive. Whether Lhx6 and -8 affect functions in tissues and organs other than neural, craniofacial, oocytes, and germ cells is largely unexplored. Taken together, Lhx6 and -8 are important regulators of cell lineage specification and may act as one of the pivotal mediators of stem cell fate. Undoubtedly, future investigations of Lhx6 and -8 biology will continue to yield fascinating insights into tissue development and homeostasis, in addition to their putative roles in tissue regeneration and ageing.-Zhou, C., Yang, G., Chen, M., He, L., Xiang, L., Ricupero, C., Mao, J. J., Ling, J. Lhx6 and Lhx8: cell fate regulators and beyond. FASEB J. 29, 4083-4091 (2015). www.fasebj.org

show abstract

“…In mice, however, the enhancer of Lhx8 , which is required for craniofacial development, contains a conserved binding site for TCF/LEF that is critical for direct control of Lhx8 expression in primary maxillary arch cells by Wnt signaling (Landin Malt et al, 2014). Whether activation of this enhancer is mediated by WNKs via effects on Wnt signaling remains to be determined.…”

Section: Emerging Functions Of the Wnk Signaling Axis In Developmentmentioning

confidence: 99%

WNK Kinases in Development and Disease

Rodan

Jenny

2017

Current Topics in Developmental Biology

View full text Add to dashboard Cite

WNK (With-No-Lysine (K)) kinases are serine-threonine kinases characterized by an atypical placement of a catalytic lysine within the kinase domain. Mutations in human WNK1 or WNK4 cause an autosomal dominant syndrome of hypertension and hyperkalemia, reflecting the fact that WNK kinases are critical regulators of renal ion transport processes. Here, the role of WNKs in the regulation of ion transport processes in vertebrate and invertebrate renal function, cellular and organismal osmoregulation, cell migration and cerebral edema will be reviewed, along with emerging literature demonstrating roles for WNKs in cardiovascular and neural development, Wnt signaling, and cancer. Conserved roles for these kinases across phyla are emphasized.

show abstract

Identification of a Face Enhancer Reveals Direct Regulation of LIM Homeobox 8 (Lhx8) by Wingless-Int (WNT)/β-Catenin Signaling

Cited by 13 publications

References 102 publications

Face morphogenesis is promoted by Pbx-dependent EMT via regulation of Snail1 during frontonasal prominence fusion

Face morphogenesis is promoted by Pbx-dependent EMT via regulation of Snail1 during frontonasal prominence fusion

Lhx6 and Lhx8: cell fate regulators and beyond

WNK Kinases in Development and Disease

Contact Info

Product

Resources

About