Six3 cooperates with Hedgehog signaling to specify ventral telencephalon by promoting early expression of Foxg1a and repressing Wnt signaling

A secreted signaling factor, Sonic hedgehog (Shh), has a crucial role in the generation of ventral cell types along the entire rostrocaudal axis of the neural tube. At caudal levels of the neuraxis, Shh is secreted by the notochord and floor plate during the period that ventral cell fates are specified. At anterior prosencephalic levels that give rise to the telencephalon, however, neither the prechordal mesoderm nor the ventral neural tube expresses Shh at the time that the overt ventral character of the telencephalon becomes evident. Thus, the precise role and timing of Shh signaling relevant to the specification of ventral telencephalic identity remains unclear. By analysing neural cell differentiation in chick neural plate explants we provide evidence that neural cells acquire molecular properties characteristic of the ventral telencephalon in response to Shh signals derived from the anterior primitive streak/Hensen's node region at gastrula stages. Exposure of prospective anterior prosencephalic cells to Shh at this early stage is sufficient to initiate a temporal program of differentiation that parallels that of neurons generated normally in the medial ganglionic eminence subdivision of the ventral telencephalon.

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The carp homeobox gene Ovx1 shows early expression during gastrulation and subsequently in the vagal lobe, the facial lobe and the ventral telencephalon

Development Genes and Evolution ◽

10.1007/s004270050154 ◽

1998 ◽

Vol 208 (1) ◽

pp. 56-59 ◽

Cited By ~ 3

Author(s):

H. W. J. Stroband ◽

Marcus P. S. Dekens ◽

Geertruy te Kronnie ◽

Henk Schipper ◽

Johannis Samallo

Keyword(s):

Homeobox Gene ◽

Ventral Telencephalon ◽

Early Expression ◽

Vagal Lobe

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The Heterotrimeric Protein Go Is Required for the Formation of Heart Epithelium in Drosophila

The Journal of Cell Biology ◽

10.1083/jcb.145.5.1063 ◽

1999 ◽

Vol 145 (5) ◽

pp. 1063-1076 ◽

Cited By ~ 49

Author(s):

F. Frémion ◽

M. Astier ◽

S. Zaffran ◽

A. Guillèn ◽

V. Homburger ◽

...

Keyword(s):

Nervous System ◽

Hedgehog Signaling ◽

Precursor Cells ◽

Epithelial Polarity ◽

Heart Tube ◽

Gene Encoding ◽

Α Subunit ◽

Vesicular Traffic ◽

Early Expression ◽

Visceral Muscles

The gene encoding the α subunit of the Drosophila Go protein is expressed early in embryogenesis in the precursor cells of the heart tube, of the visceral muscles, and of the nervous system. This early expression coincides with the onset of the mesenchymal-epithelial transition to which are subjected the cardial cells and the precursor cells of the visceral musculature. This gene constitutes an appropriate marker to follow this transition. In addition, a detailed analysis of its expression suggests that the cardioblasts originate from two subpopulations of cells in each parasegment of the dorsal mesoderm that might depend on the wingless and hedgehog signaling pathways for both their determination and specification. In the nervous system, the expression of Goα shortly precedes the beginning of axonogenesis. Mutants produced in the Goα gene harbor abnormalities in the three tissues in which the gene is expressed. In particular, the heart does not form properly and interruptions in the heart epithelium are repeatedly observed, henceforth the brokenheart (bkh) name. Furthermore, in the bkh mutant embryos, the epithelial polarity of cardial cells was not acquired (or maintained) in various places of the cardiac tube. We predict that bkh might be involved in vesicular traffic of membrane proteins that is responsible for the acquisition of polarity.

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Cleft Palate and Aglossia Result from Perturbations in Wnt and Hedgehog Signaling

The Cleft Palate-Craniofacial Journal ◽

10.1597/15-178 ◽

2017 ◽

Vol 54 (3) ◽

pp. 269-280 ◽

Cited By ~ 5

Author(s):

Gongjie Yuan ◽

Gurpreet Singh ◽

Serafine Chen ◽

Kristy Carrington Perez ◽

Yan Wu ◽

...

Keyword(s):

Cell Proliferation ◽

Wnt Signaling ◽

Primary Cilium ◽

Molecular Basis ◽

Hedgehog Signaling ◽

Intraflagellar Transport ◽

Molecular Signaling ◽

A Cell ◽

Cranial Neural Crest Cells ◽

Facial Development

Objective The objective of this study was to explore the molecular basis for cleft secondary palate and arrested tongue development caused by the loss of the intraflagellar transport protein, Kif3a. Design Kif3a mutant embryos and their littermate controls were analyzed for defects in facial development at multiple stages of embryonic development. Histology was employed to understand the effects of Kif3a deletion on palate and tongue development. Various transgenic reporter strains were used to understand how deletion of Kif3a affected Hedgehog and Wnt signaling. Immunostaining for structural elements of the tongue and for components of the Wnt pathway were performed. BrdU activity analyses were carried out to examine how the loss of Kif3a affected cell proliferation and led to palate and tongue malformations. Results Kif3a deletion causes cranial neural crest cells to become unresponsive to Hedgehog signals and hyper-responsive to Wnt signals. This aberrant molecular signaling causes abnormally high cell proliferation, but paradoxically outgrowths of the tongue and the palatal processes are reduced. The basis for this enigmatic effect can be traced back to a disruption in epithelial/mesenchymal signaling that governs facial development. Conclusion The primary cilium is a cell surface organelle that integrates Hh and Wnt signaling, and disruptions in the function of the primary cilium cause one of the most common—of the rarest—craniofacial birth defects observed in humans. The shared molecular basis for these dysmorphologies is an abnormally high Wnt signal simultaneous with an abnormally low Hedgehog signal. These pathways are integrated in the primary cilium.

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Targeting Wnt Signaling in Endometrial Cancer

Cancers ◽

10.3390/cancers13102351 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2351

Author(s):

Iram Fatima ◽

Susmita Barman ◽

Rajani Rai ◽

Kristina W. Thiel ◽

Vishal Chandra

Keyword(s):

Endometrial Cancer ◽

Wnt Signaling ◽

Hedgehog Signaling ◽

Breast Cancers ◽

Genetic Studies ◽

Wnt Proteins ◽

New Findings ◽

Endometrial Carcinomas ◽

Cycle Regulation

This review presents new findings on Wnt signaling in endometrial carcinoma and implications for possible future treatments. The Wnt proteins are essential mediators in cell signaling during vertebrate embryo development. Recent biochemical and genetic studies have provided significant insight into Wnt signaling, in particular in cell cycle regulation, inflammation, and cancer. The role of Wnt signaling is well established in gastrointestinal and breast cancers, but its function in gynecologic cancers, especially in endometrial cancers, has not been well elucidated. Development of a subset of endometrial carcinomas has been attributed to activation of the APC/β-catenin signaling pathway (due to β-catenin mutations) and downregulation of Wnt antagonists by epigenetic silencing. The Wnt pathway also appears to be linked to estrogen and progesterone, and new findings implicate it in mTOR and Hedgehog signaling. Therapeutic interference of Wnt signaling remains a significant challenge. Herein, we discuss the Wnt-activating mechanisms in endometrial cancer and review the current advances and challenges in drug discovery.

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Recent Advances in αβ T Cell Biology: Wnt Signaling, Notch Signaling, Hedgehog Signaling and Their Translational Perspective

AIMS Medical Science ◽

10.3934/medsci.2016.3.312 ◽

2016 ◽

Vol 3 (4) ◽

pp. 312-328

Author(s):

Luokun Xie ◽

◽

Wenping Lin ◽

Kai Dai

Keyword(s):

T Cell ◽

Wnt Signaling ◽

Notch Signaling ◽

Cell Biology ◽

Hedgehog Signaling ◽

Recent Advances ◽

T Cell Biology

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The Polycomb group protein Ring1 regulates dorsoventral patterning of the mouse telencephalon

Nature Communications ◽

10.1038/s41467-020-19556-5 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Hikaru Eto ◽

Yusuke Kishi ◽

Nayuta Yakushiji-Kaminatsui ◽

Hiroki Sugishita ◽

Shun Utsunomiya ◽

...

Keyword(s):

Wnt Signaling ◽

Ectopic Expression ◽

Regional Identity ◽

Polycomb Group ◽

Polycomb Group Protein ◽

Specific Expression ◽

Ventral Telencephalon ◽

Functional Regions ◽

Wnt Ligands ◽

Group Protein

Abstract Dorsal-ventral patterning of the mammalian telencephalon is fundamental to the formation of distinct functional regions including the neocortex and ganglionic eminence. While Bone morphogenetic protein (BMP), Wnt, and Sonic hedgehog (Shh) signaling are known to determine regional identity along the dorsoventral axis, how the region-specific expression of these morphogens is established remains unclear. Here we show that the Polycomb group (PcG) protein Ring1 contributes to the ventralization of the mouse telencephalon. Deletion of Ring1b or both Ring1a and Ring1b in neuroepithelial cells induces ectopic expression of dorsal genes, including those for BMP and Wnt ligands, as well as attenuated expression of the gene for Shh, a key morphogen for ventralization, in the ventral telencephalon. We observe PcG protein–mediated trimethylation of histone 3 at lysine-27 and binding of Ring1B at BMP and Wnt ligand genes specifically in the ventral region. Furthermore, forced activation of BMP or Wnt signaling represses Shh expression. Our results thus indicate that PcG proteins suppress BMP and Wnt signaling in a region-specific manner and thereby allow proper Shh expression and development of the ventral telencephalon.

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