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Individual conditions grouped according to the international nosology and classification of genetic skeletal disorders*
Published in Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow, Fetal and Perinatal Skeletal Dysplasias, 2012
Christine M Hall, Amaka C Offiah, Francesca Forzano, Mario Lituania, Michelle Fink, Deborah Krakow
Genetics: an autosomal recessive disorder. Four genes are associated with this condition and define different subtypes (1–4): DLL3 (delta-like 3), MESP2 (mesoderm posterior 2), LFNG (lunatic fringe), HES7 (hairy/enhancer of split, homolog of drosophila, 7). All these genes encode proteins involved in the notch-signalling pathway, crucial to normal somitogenesis. DLL3 is a notch ligand and is crucial in the cell-signalling processes which generate rostro–caudal somite boundary formation with a defined temporal periodicity driven by the molecular ‘segmentation clock’. MESP2 is a member of the basic helix-loop-helix (bHLH) family of transcriptional regulatory proteins. LFNG is a glycosyltransferase; it localises to the Golgi and post-translationally modifies the notch family receptors. Its expression is indirectly regulated by DLL3. HES7 encodes a bHLH-orange domain transcriptional repressor protein. In the mouse, HES genes are direct targets of notch and repress their own transcription through the interaction with their own promoters; due to their very short half-lives, cyclic waves of transcription are generated every 90–120 minutes. A rare form of SCD with autosomal dominant inheritance has been reported, the gene is still unknown.
Sacrococcygeal teratoma
Published in Prem Puri, Newborn Surgery, 2017
A sacrococcygeal teratoma (SCT) is a neoplasm arising from the caudal end of the spine, usually protruding from the inferior end of the infant’s spinal column and displacing the anus forward. These tumors have a female-to-male ratio of at least 3:1.1–9 The incidence is approximately 1 in 40,000 live births,10,11 although a recent article from Finland12 found a prevalence of 1:14,900 in a study that ascertained the prevalence in the total population, including terminations of pregnancies and stillbirths. There is general agreement that SCT is the result of continued multiplication of totipotent cells from Hensen’s node that fail to apoptose at the end of embryonic life.7,13,14 This concept has received support from the work of Busch et al.,15 who have identified histochemical markers in SCTs supporting an origin from caudal embryonic stem cells. This provides convincing evidence against the theory that these tumors arise from migrating germ cells travelling from yolk sac to gonad. Economou et al.16 recently reported a series of experiments in mice exploring the results of injecting pluripotent cells into early embryos. They found that expression of Oct4 and Nanog in the primitive streak/tail bud after the start of somitogenesis does not result in neoplasia. Most authorities reject the concept that these are suppressed twins or parasitic fetuses. In 1976, Pantoja and Rodriguez-Ibanez17 reviewed the conflicting theories as to the origin of these tumors. Their findings still stand. Clearly, more studies are needed to determine the genetic influences that are associated with the formation of SCTs.
The role of the Notch pathway in the pathogenesis of systemic sclerosis: clinical implications
Published in Expert Review of Clinical Immunology, 2021
Filipe Seguro Paula, José Delgado Alves
The Notch signaling pathway is an ancient one in the evolution of living organisms. Its origins revolve around the emergence of multicellular life forms and is present in all metazoans. This reflects its importance to life: it is a system used to coordinate the actions of neighboring cells, both during development and adult life, and acts through the direct contact between cells. During somitogenesis, where a spatial pattern emerges from an undifferentiated group of cells, Notch signaling is a central player in defining distinct cellular territories [9]. Pivotal roles have been described in many other stages of development in almost every tissue and organ [10]. In this regard, one can classify its function into two recognizable strategies: lateral inhibition and inductive signaling. Regarding lateral inhibition, Notch signaling acts to ensure that two adjacent cells will have different behaviors or different differentiation programs. In neural development, for example, each cell with its neural differentiation program set in place will express Notch ligands at the membrane, which will in turn activate Notch receptors and subsequent signaling in all neighboring cells, blocking their differentiation into neurons and directing them to be glial cells [10]. In turn, Notch activation in neighboring cells will down-regulate the expression of Notch ligands, preventing them to activate Notch receptors in the central cell. In this way, it is ensured that neurons are covered by glial cells. Conversely, in inductive signaling Notch activation in one cell will induce the same expression in the neighboring cells, which will in turn increase the expression of Notch ligands, effectively enhancing Notch activation on the next group of cells [9].
Impact of vitamin deficiency on microbiota composition and immunomodulation: relevance to autistic spectrum disorders
Published in Nutritional Neuroscience, 2021
Roberta Ribeiro, Jacques Robert Nicoli, Gesivaldo Santos, Jane Lima-Santos
Retinoic acid (RA), which is obtained mainly from diet [24], is a major active product of vitamin A (retinol) and was considered a neuroactive steroid [25]. In neurodevelopment, RA contributes to somitogenesis, development of the neural tube and neural plate, gene activation for cellular differentiation of glial cells and somatosensory neurons, such as the ocular and motor neurons [30,31]. Low or high RA concentration during the development of the CNS can induce teratogenic effects by decreased expression of the RA-related orphan receptor alfa (RORA) and low expression of structural genes, such as the Homeobox family (HOXA-1, HOXb5a, HOXb6b) [3233–34].
A review of the hemivertebrae and hemivertebra resection
Published in British Journal of Neurosurgery, 2022
Beixi Bao, Hui Yan, Jiaguang Tang
Failure of formation or segmentation during somitogenesis has been proposed as a cause of HV. Notch, FGF, and Wnt signaling pathways have been shown to participate in the pathogenesis of somitogenesis.2 Associations with Carbon Monoxide exposure, maternal diabetes, and anti-epileptic drugs have also been proposed as possible causes.3 Previous cases of congenital scoliosis in non-identical4 and identical twins5 have been reported in the literature and it appears to be more common in girls than in boys. The familial incidence rate is approximately 1–5%.6,7