scholarly journals The Role of Sonic Hedgehog in Human Holoprosencephaly and Short-Rib Polydactyly Syndromes

2021 ◽  
Vol 22 (18) ◽  
pp. 9854
Author(s):  
Christine Loo ◽  
Michael Pearen ◽  
Grant Ramm
Keyword(s):  
Human Development ◽  
Sonic Hedgehog ◽  
Mammalian Cells ◽  
Animal Studies ◽  
Primary Cilia ◽  
Genetic Mutation ◽  
Wide Variability ◽  
Using Data ◽  
Differentiation And Proliferation

The Hedgehog (HH) signalling pathway is one of the major pathways controlling cell differentiation and proliferation during human development. This pathway is complex, with HH function influenced by inhibitors, promotors, interactions with other signalling pathways, and non-genetic and cellular factors. Many aspects of this pathway are not yet clarified. The main features of Sonic Hedgehog (SHH) signalling are discussed in relation to its function in human development. The possible role of SHH will be considered using examples of holoprosencephaly and short-rib polydactyly (SRP) syndromes. In these syndromes, there is wide variability in phenotype even with the same genetic mutation, so that other factors must influence the outcome. SHH mutations were the first identified genetic causes of holoprosencephaly, but many other genes and environmental factors can cause malformations in the holoprosencephaly spectrum. Many patients with SRP have genetic defects affecting primary cilia, structures found on most mammalian cells which are thought to be necessary for canonical HH signal transduction. Although SHH signalling is affected in both these genetic conditions, there is little overlap in phenotype. Possible explanations will be canvassed, using data from published human and animal studies. Implications for the understanding of SHH signalling in humans will be discussed.

Role of Education in Inter-Caste Marriages of Women from Scheduled Castes in India

2019 ◽  
Vol 2 (2) ◽  
pp. 79-86
Author(s):  
Ravindra Medhe
Keyword(s):  
Social Change ◽  
Human Development ◽  
Social Cohesion ◽  
Negative Relationship ◽  
Freedom Of Choice ◽  
Large Scope ◽  
Scheduled Castes ◽  
Using Data ◽  
The Relationship

Scheduled Castes (SC) is a group of deprived castes in India. Traditionally, people belongs to these castes are socio-economically exploited and untouchables. The present study analyses the role of education in decision of inter-caste marriages for social cohesion. The relationship between education of bride, parents and parents-in-law with number of inter-caste marriages was calculated using data compiled by India Human Development Survey (2011). The study shows no direct and robust relationship between education and inter-caste marriages. Educated brides lead for inter-caste marriages and educated parents support in this decision, but negative relationship was observed for education of parents-in-law with number of inter-caste marriages. Educated parents-in-law show no acceptance for inter-caste marriages of their shoots. The freedom of choice to bride show key role in formation of inter-case marriages which shows wide state-to-state variations. Education improves the capabilities of a person to deicide their own. Therefore, we have large scope to create bases for inter-caste marriages and social change through enlightenment and education.

scholarly journals The Ciliopathy Gene Ftm/Rpgrip1l Controls Mouse Forebrain Patterning via Region-Specific Modulation of Hedgehog/Gli Signaling

2018 ◽  
Author(s):  
Abraham Andreu-Cervera ◽  
Isabelle Anselme ◽  
Alice Karam ◽  
Martin Catala ◽  
Sylvie Schneider-Maunoury
Keyword(s):  
Sonic Hedgehog ◽  
Primary Cilia ◽  
System Development ◽  
Critical Role ◽  
Ground Level ◽  
Nervous System Development ◽  
Gli Transcription Factors ◽  
Optic Vesicles ◽  
Specific Control

ABSTRACTPrimary cilia are essential for central nervous system development. In the mouse, they play a critical role in patterning the spinal cord and telencephalon via the regulation of Hedgehog/Gli signaling. However, despite the frequent disruption of this signaling pathway in human forebrain malformations, the role of primary cilia in forebrain morphogenesis has been little investigated outside the telencephalon. Here we studied development of the diencephalon, hypothalamus and eyes in mutant mice in which the Ftm/Rgprip1l ciliopathy gene is disrupted. At the end of gestation, Ftm-/- fetuses displayed anophthalmia, a reduction of the ventral hypothalamus and a disorganization of diencephalic nuclei and axonal tracts. In Ftm-/- embryos, we found that the ventral forebrain structures and the rostral thalamus were missing. Optic vesicles formed but lacked the optic cups. We analyzed the molecular causes of these defects. In Ftm-/- embryos, Sonic hedgehog (Shh) expression was lost in the ventral forebrain but maintained in the zona limitans intrathalamica (ZLI), the mid-diencephalic organizer. In the diencephalon, Gli activity was dampened in regions adjacent to the Shh-expressing ZLI but displayed a higher Hh-independent ground level in the other regions. Our data uncover a complex role of cilia in development of the diencephalon, hypothalamus and eyes via the region-specific control of the ratio of activator and repressor forms of the Gli transcription factors. They call for a closer examination of forebrain defects in severe ciliopathies and for a search for ciliopathy genes as modifiers in other human conditions with forebrain defects.

Functional association of retinoic acid and hedgehog signaling in Xenopus primary neurogenesis

Development ◽  
1999 ◽  
Vol 126 (19) ◽  
pp. 4257-4265 ◽  
Author(s):  
P.G. Franco ◽  
A.R. Paganelli ◽  
S.L. Lopez ◽  
A.E. Carrasco
Keyword(s):  
Retinoic Acid ◽  
Sonic Hedgehog ◽  
Hedgehog Signaling ◽  
Inhibitory Effect ◽  
Neural Plate ◽  
Neural Ectoderm ◽  
Differentiation And Proliferation ◽  
Primary Neurogenesis ◽  
Xenopus Laevis Embryos

Previous work has shown that the posteriorising agent retinoic acid can accelerate anterior neuronal differentiation in Xenopus laevis embryos (Papalopulu, N. and Kintner, C. (1996) Development 122, 3409–3418). To elucidate the role of retinoic acid in the primary neurogenesis cascade, we investigated whether retinoic acid treatment of whole embryos could change the spatial expression of a set of genes known to be involved in neurogenesis. We show that retinoic acid expands the N-tubulin, X-ngnr-1, X-MyT1, X-Δ-1 and Gli3 domains and inhibits the expression of Zic2 and sonic hedgehog in the neural ectoderm, whereas a retinoid antagonist produces opposite changes. In contrast, sonic and banded hedgehog overexpression reduced the N-tubulin stripes, enlarged the neural plate at the expense of the neural crest, downregulated Gli3 and upregulated Zic2. Thus, retinoic acid and hedgehog signaling have opposite effects on the prepattern genes Gli3 and Zic2 and on other genes acting downstream in the neurogenesis cascade. In addition, retinoic acid cannot rescue the inhibitory effect of Notch(ICD), Zic2 or sonic hedgehog on primary neurogenesis. Our results suggest that retinoic acid acts very early, upstream of sonic hedgehog, and we propose a model for regulation of differentiation and proliferation in the neural plate, showing that retinoic acid might be activating primary neurogenesis by repressing sonic hedgehog expression.

scholarly journals The heteromeric PC-1/PC-2 polycystin complex is activated by the PC-1 N-terminus

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Kotdaji Ha ◽  
Mai Nobuhara ◽  
Qinzhe Wang ◽  
Rebecca V Walker ◽  
Feng Qian ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Primary Cilia ◽  
N Terminus ◽  
Functional Understanding ◽  
Soluble Ligand ◽  
Autosomal Dominant Polycystic Kidney ◽  
Necessary And Sufficient ◽  
Autoproteolytic Cleavage

Mutations in the polycystin proteins, PC-1 and PC-2, result in autosomal dominant polycystic kidney disease (ADPKD) and ultimately renal failure. PC-1 and PC-2 enrich on primary cilia, where they are thought to form a heteromeric ion channel complex. However, a functional understanding of the putative PC-1/PC-2 polycystin complex is lacking due to technical hurdles in reliably measuring its activity. Here we successfully reconstitute the PC-1/PC-2 complex in the plasma membrane of mammalian cells and show that it functions as an outwardly rectifying channel. Using both reconstituted and ciliary polycystin channels, we further show that a soluble fragment generated from the N-terminal extracellular domain of PC-1 functions as an intrinsic agonist that is necessary and sufficient for channel activation. We thus propose that autoproteolytic cleavage of the N-terminus of PC-1, a hotspot for ADPKD mutations, produces a soluble ligand in vivo. These findings establish a mechanistic framework for understanding the role of PC-1/PC-2 heteromers in ADPKD and suggest new therapeutic strategies that would expand upon the limited symptomatic treatments currently available for this progressive, terminal disease.

Knowledge, Local Development, and Urbanization in Arab Economies

2014 ◽  
pp. 104-123
Author(s):  
Nada Zouag ◽  
Ahmed Driouchi
Keyword(s):  
Regression Analysis ◽  
Human Development ◽  
Knowledge Economy ◽  
Local Development ◽  
Current Situation ◽  
Descriptive Statistics ◽  
Global Knowledge ◽  
Using Data ◽  
Development Prospects

In the absence of local knowledge measures, this chapter looks at how local universities and research centers could explain the potential for local development in territorial communities. This chapter also assesses the links between urbanization and development. It is mainly based on the review of literature, descriptive statistics, and regression analysis using data on local development, urbanization, global knowledge measures, and human development indices. The focus here is on Arab economies. The current situation and development prospects are discussed in relation to the role of knowledge economy in local development but also in further urbanization. Smart, livable, and inclusive cities are discussed.

Critical Implications of the Role of Play in Human Development

PsycCRITIQUES ◽  
2010 ◽  
Vol 55 (7) ◽  
Author(s):  
Sherri McCarthy ◽  
Yolanda Mora ◽  
Albertina Aros
Keyword(s):  
Human Development

INOVASI PEMBELAJARAN AKIDAH AKHLAK MENGGUNAKAN METODE ROLE PLAY DALAM MENINGKATKAN PRESTASI BELAJAR SISWA

2018 ◽  
Vol 2 (1) ◽  
pp. 52-63
Author(s):  
Ansori Ansori
Keyword(s):  
Data Reduction ◽  
Role Play ◽  
Learning Goals ◽  
New Paradigm ◽  
Learning Materials ◽  
Analysis Technique ◽  
Flexible Schedule ◽  
Using Data ◽  
Real Action

The use of various methods will greatly help students in achieving learning goals. As role play method is one way mastery of learning materials through the development of imagination and appreciation of students on learning materials. Data collection techniques in this study are observation, interviews, and documentation. To analyze the data in this research using data analysis technique of Miles and Huberman model that is data reduction (Data Reduction), data presentation (Data Display) and conclusion (Conclution Drawing / verification) The findings in this research is innovation of role play method can change paradigm to the new paradigm so that the role of the teacher is more as a facilitator, counselor, consultant, and comrade study Flexible schedule, open as needed Learning directed by students themselves Problem-based, project, real world, real action, and reflection Design and investigation. Computers as tools, and dynamic media presentations.

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