Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon

The telencephalon has two major subdivisions, the pallium and subpallium. The pallium, which primarily consists of glutamatergic cortical structures, expresses dorsal molecular markers, whereas the subpallium, which primarily consists of the GABAergic basal ganglia, expresses ventral molecular markers. Here, we present evidence that the progenitor and postmitotic cells flanking the pallial/subpallial boundary (PSB) in the embryonic mouse can be subdivided into multiple regions that express unique combinations of transcription factors. The domains that immediately flank the PSB are the ventral pallium (VP) and the dorsal lateral ganglionic eminence (dLGE). The early expression of the Pax6 and Gsh2 homeobox transcription factors overlaps in the region of the dLGE. Analyses of mice that lack functional alleles of either Gsh2 or Pax6 demonstrate that these genes have complementary roles in patterning the primordia flanking the PSB. In the Gsh2 mutants, the dLGE is respecified into a VP-like structure, whereas in the Pax6 mutants the VP is respecified into a dLGE-like structure. The role of Pax6 in dorsalizing the telencephalon is similar to its role in the spinal cord, supporting the hypothesis that some dorsoventral patterning mechanisms are used at all axial levels of the central nervous system.

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The role of Xenopus dickkopf1 in prechordal plate specification and neural patterning

Development ◽

10.1242/dev.127.22.4981 ◽

2000 ◽

Vol 127 (22) ◽

pp. 4981-4992 ◽

Cited By ~ 8

Author(s):

O. Kazanskaya ◽

A. Glinka ◽

C. Niehrs

Keyword(s):

Target Genes ◽

Loss Of Function ◽

Dorsoventral Patterning ◽

Gastrula Stage ◽

Neural Patterning ◽

Prechordal Plate ◽

Wnt Inhibitor ◽

The Central Nervous System ◽

Wnt Inhibitors

Dickkopf1 (dkk1) encodes a secreted WNT inhibitor expressed in Spemann's organizer, which has been implicated in head induction in Xenopus. Here we have analyzed the role of dkk1 in endomesoderm specification and neural patterning by gain- and loss-of-function approaches. We find that dkk1, unlike other WNT inhibitors, is able to induce functional prechordal plate, which explains its ability to induce secondary heads with bilateral eyes. This may be due to differential WNT inhibition since dkk1, unlike frzb, inhibits Wnt3a signalling. Injection of inhibitory antiDkk1 antibodies reveals that dkk1 is not only sufficient but also required for prechordal plate formation but not for notochord formation. In the neural plate dkk1 is required for anteroposterior and dorsoventral patterning between mes- and telencephalon, where dkk1 promotes anterior and ventral fates. Both the requirement of anterior explants for dkk1 function and their ability to respond to dkk1 terminate at late gastrula stage. Xenopus embryos posteriorized with bFGF, BMP4 and Smads are rescued by dkk1. dkk1 does not interfere with the ability of bFGF to induce its immediate early target gene Xbra, indicating that its effect is indirect. In contrast, there is cross-talk between BMP and WNT signalling, since induction of BMP target genes is sensitive to WNT inhibitors until the early gastrula stage. Embryos treated with retinoic acid (RA) are not rescued by dkk1 and RA affects the central nervous system (CNS) more posterior than dkk1, suggesting that WNTs and retinoids may act to pattern anterior and posterior CNS, respectively, during gastrulation.

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MiR193a Modulation and Podocyte Phenotype

Cells ◽

10.3390/cells9041004 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1004

Author(s):

Alok Jha ◽

Shourav Saha ◽

Kamesh Ayasolla ◽

Himanshu Vashistha ◽

Ashwani Malhotra ◽

...

Keyword(s):

Transcription Factors ◽

Molecular Markers ◽

Promoter Region ◽

Therapeutic Strategy ◽

Protein Complexes ◽

Md Simulations ◽

Tertiary Structures ◽

Docking Approach ◽

Apolipoprotein L1

Apolipoprotein L1 (APOL1)-miR193a axis has been reported to play a role in the maintenance of podocyte homeostasis. In the present study, we analyzed transcription factors relevant to miR193a in human podocytes and their effects on podocytes’ molecular phenotype. The motif scan of the miR193a gene provided information about transcription factors, including YY1, WT1, Sox2, and VDR-RXR heterodimer, which could potentially bind to the miR193a promoter region to regulate miR193a expression. All structure models of these transcription factors and the tertiary structures of the miR193a promoter region were generated and refined using computational tools. The DNA-protein complexes of the miR193a promoter region and transcription factors were created using a docking approach. To determine the modulatory role of miR193a on APOL1 mRNA, the structural components of APOL1 3’ UTR and miR193a-5p were studied. Molecular Dynamic (MD) simulations validated interactions between miR193a and YY1/WT1/Sox2/VDR/APOL1 3′ UTR region. Undifferentiated podocytes (UPDs) displayed enhanced miR193a, YY1, and Sox2 but attenuated WT1, VDR, and APOL1 expressions, whereas differentiated podocytes (DPDs) exhibited attenuated miR193a, YY1, and Sox2 but increased WT1, VDR, APOL1 expressions. Inhibition of miR193a in UPDs enhanced the expression of APOL1 as well as of podocyte molecular markers; on the other hand, DPD-transfected with miR193a plasmid showed downing of APOL1 as well as podocyte molecular markers suggesting a causal relationship between miR193a and podocyte molecular markers. Silencing of YY1 and Sox2 in UPDs decreased the expression of miR193a but increased the expression of VDR, and CD2AP (a marker of DPDs); in contrast, silencing of WT1 and VDR in DPDs enhanced the expression of miR193a, YY1, and Sox2. Since miR193a-downing by Vitamin D receptor (VDR) agonist not only enhanced the mRNA expression of APOL1 but also of podocyte differentiating markers, suggest that down-regulation of miR193a could be used to enhance the expression of podocyte differentiating markers as a therapeutic strategy.

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The Role of the FOXP Family of Transcription Factors in ASD

Disease Markers ◽

10.1155/2012/456787 ◽

2012 ◽

Vol 33 (5) ◽

pp. 251-260 ◽

Cited By ~ 34

Author(s):

J. Michael Bowers ◽

Genevieve Konopka

Keyword(s):

Transcription Factors ◽

Animal Behavior ◽

Autism Spectrum ◽

Evolution Of Language ◽

Complex Genetics ◽

Neurodevelopmental Disease ◽

Key Players ◽

The Central Nervous System ◽

Spectrum Disorders

Autism spectrum disorders (ASD) is a neurodevelopmental disease with complex genetics; however, the genes that are responsible for this disease still remain mostly unknown. Here, we focus on the FOXP family of transcription factors as there is emerging evidence strongly linking these genes to ASD and other genes implicated in ASD. The FOXP family of genes includes three genes expressed in the central nervous system: FOXP1, FOPX2, and FOXP4. This unique group of transcription factors has known functions in brain development as well as the evolution of language. We will also discuss the other genes including transcriptional targets of FOXP genes that have been found to be associated with language and may be important in the pathophysiology of ASD. Finally, we will review the emerging animal models currently being used to study the function of the FOXP genes within the context of ASD symptomology. The combination of gene expression and animal behavior is critical for elucidating how genes such as the FOXP family members are key players within the framework of the developing brain.

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Formation of neuroblasts in the embryonic central nervous system of Drosophila melanogaster is controlled by SoxNeuro

Development ◽

10.1242/dev.129.18.4193 ◽

2002 ◽

Vol 129 (18) ◽

pp. 4193-4203 ◽

Cited By ~ 5

Author(s):

Marita Buescher ◽

Fook Sion Hing ◽

William Chia

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Transcription Factors ◽

Neural Progenitor Cells ◽

Loss Of Function ◽

Dorsoventral Patterning ◽

Sox Proteins ◽

The Central Nervous System ◽

Modulation Of Gene Expression ◽

Determining Factor

Sox proteins form a family of HMG-box transcription factors related to the mammalian testis determining factor SRY. Sox-mediated modulation of gene expression plays an important role in various developmental contexts. Drosophila SoxNeuro, a putative ortholog of the vertebrate Sox1, Sox2 and Sox3 proteins, is one of the earliest transcription factors to be expressed pan-neuroectodermally. We demonstrate that SoxNeuro is essential for the formation of the neural progenitor cells in central nervous system. We show that loss of function mutations of SoxNeuro are associated with a spatially restricted hypoplasia: neuroblast formation is severely affected in the lateral and intermediate regions of the central nervous system, whereas ventral neuroblast formation is almost normal. We present evidence that a requirement for SoxNeuro in ventral neuroblast formation is masked by a functional redundancy with Dichaete, a second Sox protein whose expression partially overlaps that of SoxNeuro. Genetic interactions of SoxNeuro and the dorsoventral patterning genes ventral nerve chord defective and intermediate neuroblasts defective underlie ventral and intermediate neuroblast formation. Finally, the expression of the Achaete-Scute gene complex suggests that SoxNeuro acts upstream and in parallel with the proneural genes.

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Role of Forkhead Transcription Factors of the O Class (FoxO) in Development and Progression of Alzheimer’s Disease

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666201001105553 ◽

2020 ◽

Vol 19 (9) ◽

pp. 709-721

Author(s):

Shikha Goswami ◽

Ozaifa Kareem ◽

Ramesh K. Goyal ◽

Sayed M. Mumtaz ◽

Rajiv K. Tonk ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transcription Factors ◽

Neurological Disorders ◽

The United States ◽

Forkhead Transcription Factors ◽

The Central Nervous System ◽

Degenerative Disorder ◽

The Brain

: In the central nervous system (CNS), a specific loss of focal neurons leads to mental and neurological disorders like dementia, Alzheimer’s disease (AD), Huntington’s disease, Parkinson’s disease, etc. AD is a neurological degenerative disorder, which is progressive and irreversible in nature and is the widely recognized reason for dementia in the geriatric populace. It affects 10% of people above the age of 65 and is the fourth driving reason for death in the United States. Numerous evidence suggests that the neuronal compartment is not the only genesis of AD, but transcription factors also hold significant importance in the occurrence and advancement of the disease. It is the need of the time to find the novel molecular targets and new techniques for treating or slowing down the progression of neurological disorders, especially AD. In this article, we summarised a conceivable association between transcriptional factors and their defensive measures against neurodegeneration and AD. The mammalian forkhead transcription factors of the class O (FoxO) illustrate one of the potential objectives for the development of new methodologies against AD and other neurocognitive disorders. The presence of FoxO is easily noticeable in the “cognitive centers” of the brain, specifically in the amygdala, hippocampus, and the nucleus accumbens. FoxO proteins are the prominent and necessary factors in memory formation and cognitive functions. FoxO also assumes a pertinent role in the protection of multiple cells in the brain by controlling the involving mechanism of autophagy and apoptosis and also modulates the process of phosphorylation of the targeted protein, thus FoxO must be a putative target in the mitigation of AD. This review features the role of FoxO as an important biomarker and potential new targets for the treatment of AD.

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The Role of Neurod Genes in Brain Development, Function, and Disease

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.662774 ◽

2021 ◽

Vol 14 ◽

Author(s):

Svetlana Tutukova ◽

Victor Tarabykin ◽

Luis R. Hernandez-Miranda

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Transcription Factors ◽

Postnatal Life ◽

Neural Lineage ◽

Helix Loop Helix ◽

The Central Nervous System ◽

Bhlh Factors ◽

And Function

Transcriptional regulation is essential for the correct functioning of cells during development and in postnatal life. The basic Helix-loop-Helix (bHLH) superfamily of transcription factors is well conserved throughout evolution and plays critical roles in tissue development and tissue maintenance. A subgroup of this family, called neural lineage bHLH factors, is critical in the development and function of the central nervous system. In this review, we will focus on the function of one subgroup of neural lineage bHLH factors, the Neurod family. The Neurod family has four members: Neurod1, Neurod2, Neurod4, and Neurod6. Available evidence shows that these four factors are key during the development of the cerebral cortex but also in other regions of the central nervous system, such as the cerebellum, the brainstem, and the spinal cord. We will also discuss recent reports that link the dysfunction of these transcription factors to neurological disorders in humans.

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Axial mesendoderm refines rostrocaudal pattern in the chick nervous system

Development ◽

10.1242/dev.126.13.2921 ◽

1999 ◽

Vol 126 (13) ◽

pp. 2921-2934 ◽

Cited By ~ 2

Author(s):

A.M. Rowan ◽

C.D. Stern ◽

K.G. Storey

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Molecular Markers ◽

Regional Differences ◽

Normal Development ◽

De Novo ◽

Neural Plate ◽

Large Panel ◽

The Central Nervous System

There has long been controversy concerning the role of the axial mesoderm in the induction and rostrocaudal patterning of the vertebrate nervous system. Here we investigate the neural inducing and regionalising properties of defined rostrocaudal regions of head process/prospective notochord in the chick embryo by juxtaposing these tissues with extraembryonic epiblast or neural plate explants. We localise neural inducing signals to the emerging head process and using a large panel of region-specific neural markers, show that different rostrocaudal levels of the head process derived from headfold stage embryos can induce discrete regions of the central nervous system. However, we also find that rostral and caudal head process do not induce expression of any of these molecular markers in explants of the neural plate. During normal development the head process emerges beneath previously induced neural plate, which we show has already acquired some rostrocaudal character. Our findings therefore indicate that discrete regions of axial mesendoderm at headfold stages are not normally responsible for the establishment of rostrocaudal pattern in the neural plate. Strikingly however, we do find that caudal head process inhibits expression of rostral genes in neural plate explants. These findings indicate that despite the ability to induce specific rostrocaudal regions of the CNS de novo, signals provided by the discrete regions of axial mesendoderm do not appear to establish regional differences, but rather refine the rostrocaudal character of overlying neuroepithelium.

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