The role of Shh signalling pathway in central nervous system development and related diseases

Li, Xiaoying; Li, Yunxiao; Li, Shuanqing; Li, Han; Yang, Ciqing; Lin, Juntang

doi:10.1002/cbf.3582

Cited by 49 publications

(38 citation statements)

References 110 publications

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“…Of those, five genes may be of particular interest because they are highly expressed in the brain and are also nominally associated with brain volumes. Zinc finger protein 521 (encoded by ZNF521), a protein acting as transcriptional factor, is involved in the sonic hedgehog pathway; this pathway has an essential role in the central nervous system development (Li et al, 2020;Matsubara et al, 2009;Scicchitano et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Localizing genomic regions contributing to the extremes of externalizing behavior: ADHD, aggressive and antisocial behaviors

Lopez

Pol

Franke

et al. 2019

Preprint

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Background:Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder. ADHD co-morbidities cover a broad range of traits, including aggressive behavior (AGG) and antisocial behavior (ASB). Genetics has a high percentage on the heritability of the three traits, mainly attributed to large numbers of common variants (SNPs)with very small effect sizes. We believe that some of this common variants could give insights to other elements overlapping between ADHD, AGG and ASB. Therefore, we worked at regions where these variants group are, tested how some of these regions contribute and looked for candidate genes within these. Methods:We tested for genome-wide genetic correlations using LD score regression analysis (LDSC), followed by analyses for local SNP-based heritability and cross-trait analyses for local genetic correlations. Propective genes were followed up by further investigations of gene expression patterns and genetic associations with structural subcortical brain volumes.Results: ADHD, AGG and ASB showed global positive genetic correlations among them, but also with neuroticism. Negative global genetic correlations were observed between ADHD, AGG, ASB and Primary Sclerosing Cholangitis. At the locus level, large heterogeneity between regions was observed. Cross-trait comparisons revealed 53 shared loci of interest and prioritized 20 genes which are expressed in the human brain and showed association with subcortical brain volumes. Conclusions:This study emphasizes the importance of investigating shared genetic effects between correlated traits at the locus level. Converging evidence from different cross-trait analyses approaches highlights novel candidate genes underlying the shared biological mechanisms of ADHD, AGG and ASB.

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Section: Discussionmentioning

confidence: 99%

Localizing genomic regions contributing to the extremes of externalizing behavior: ADHD, aggressive and antisocial behaviors

Lopez

Pol

Franke

et al. 2019

Preprint

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“…SLOS is characterized by elevated 7dehydrocholesterol and low plasma cholesterol levels. Some of the major consequences of cholesterol deficiency include abnormal formation of the CNS, face and limbs via an effect on sonic hedgehog (SHH) signaling pathways during development (Li et al, 2020) and its effect on steroidogenesis, particularly that of dihydrotestosterone. Therapeutic intervention with supplementation of cholesterol and symptomatic treatment after early diagnosis decreases mortality and improves longterm outcome (Donoghue et al, 2018).…”

Section: Smith-lemli-opitz Syndromementioning

confidence: 99%

Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention

et al. 2021

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Increasing evidence suggests that the autism spectrum disorder (ASD) may be associated with inborn errors of metabolism, such as disorders of amino acid metabolism and transport [phenylketonuria, homocystinuria, S-adenosylhomocysteine hydrolase deficiency, branched-chain α-keto acid dehydrogenase kinase deficiency, urea cycle disorders (UCD), Hartnup disease], organic acidurias (propionic aciduria, L-2 hydroxyglutaric aciduria), cholesterol biosynthesis defects (Smith-Lemli-Opitz syndrome), mitochondrial disorders (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes—MELAS syndrome), neurotransmitter disorders (succinic semialdehyde dehydrogenase deficiency), disorders of purine metabolism [adenylosuccinate lyase (ADSL) deficiency, Lesch-Nyhan syndrome], cerebral creatine deficiency syndromes (CCDSs), disorders of folate transport and metabolism (cerebral folate deficiency, methylenetetrahydrofolate reductase deficiency), lysosomal storage disorders [Sanfilippo syndrome, neuronal ceroid lipofuscinoses (NCL), Niemann-Pick disease type C], cerebrotendinous xanthomatosis (CTX), disorders of copper metabolism (Wilson disease), disorders of haem biosynthesis [acute intermittent porphyria (AIP)] and brain iron accumulation diseases. In this review, we briefly describe etiology, clinical presentation, and therapeutic principles, if they exist, for these conditions. Additionally, we suggest the primary and elective laboratory work-up for their successful early diagnosis.

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“…Throughout vertebrates’ CNS development, Shh is required and acts as a morphogenic factor in proliferation, differentiation, and survival of neural precursor cells [ 68 ]. In the brain, Shh protein is first expressed ventrally at the early development stages [ 69 , 70 ].…”

Section: Lncrnas and Pathways Involved In Non-syndromic Intellectumentioning

confidence: 99%

“…In the brain, altered regulations of the Shh signaling can lead to an extensive range of neurological disorders, brain tumors, and intellectual disability [ 73 , 74 ]. Variants in the Shh gene have also been found in patients showing development abnormalities, and speech and learning delays [ 70 , 75 ]. Several non-coding RNAs have been reported as having a role of regulation of the Shh pathway, including lncRNAs, which were shown to function in modulation of neural development and differentiation, with possible effect in the intellectual disability phenotype [ 76 ].…”

Section: Lncrnas and Pathways Involved In Non-syndromic Intellectumentioning

confidence: 99%

Non-Syndromic Intellectual Disability and Its Pathways: A Long Noncoding RNA Perspective

Barros

Leão

Santis

et al. 2021

ncRNA

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Non-syndromic intellectual disability (NS-ID or idiopathic) is a complex neurodevelopmental disorder that represents a global health issue. Although many efforts have been made to characterize it and distinguish it from syndromic intellectual disability (S-ID), the highly heterogeneous aspect of this disorder makes it difficult to understand its etiology. Long noncoding RNAs (lncRNAs) comprise a large group of transcripts that can act through various mechanisms and be involved in important neurodevelopmental processes. In this sense, comprehending the roles they play in this intricate context is a valuable way of getting new insights about how NS-ID can arise and develop. In this review, we attempt to bring together knowledge available in the literature about lncRNAs involved with molecular and cellular pathways already described in intellectual disability and neural function, to better understand their relevance in NS-ID and the regulatory complexity of this disorder.

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The role of Shh signalling pathway in central nervous system development and related diseases

Cited by 49 publications

References 110 publications

Localizing genomic regions contributing to the extremes of externalizing behavior: ADHD, aggressive and antisocial behaviors

Localizing genomic regions contributing to the extremes of externalizing behavior: ADHD, aggressive and antisocial behaviors

Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention

Non-Syndromic Intellectual Disability and Its Pathways: A Long Noncoding RNA Perspective

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