Mengenal Spina Bifida dan Pencegahannya

Neural tube defects (NTD) are one of the birth defects or congenital abnormalities that occur in the brain and spine, and commonly find in newborns worldwide. Anencephaly and spina bifida are the two prevalent forms of NTD. The incidence of spina bifida happen on average 1 in 1000 cases of birth worldwide and there are 140,000 cases per year worldwide. Source searches were carried out on the online portal of journal publications as many as 20 sources from MedScape, Google Scholar and the Nation Center for Biotechnology Information / NCBI with the keywords “Neural tube defects (NTD), prevention, and spina bifida”. Spina bifida is a congenital abnormality that occurs in the womb due to a failure of closing process the neural tube during the first few weeks of embryonic development which causes the spine not completely close around the developing spinal cord nerves. NTD can ensue multifactorial conditions such as genetic, environmental, and folate deficiency. The use of folic acid supplementation starting at least 3 months before pregnancy, those are 400 mcg (0.4 mg) per day and 800 mcg per day during pregnancy can reduce the risk of developing neural tube defects such as spina bifida. Generally, spina bifida is undertaking by surgery and the regulation of patients comorbid. Public can find out prevention to avoid or reduce the risk of spina bifida so that the incidence of spina bifida can decrease along with the increasing awareness of the community regarding this disease.

Effect of Prenatal Administration of Retinoic Acid on Developing Spinal Cord of Albino Rats

Background Vitamin A and its derivatives (Retinoids) are essential for both normal embryonic development and maintenance of differentiation.Retinoids is a well-known teratogen when administered to embryos Aim to investigate the structural changes induced by prenatal administration of vitamin A on the developing spinal cord of albino rats. Material and methods forty pregnant albino rats were exposed to variable doses of vitamin A (retinylpalmitate) on gd 10.The pregnant albino rats were divided into three groups: Group I (control): rats received sesame oil by oral gavagedaily, till date of delivery. Group II (minimum therapeutic dose): rats were given retinylpalmitate 50 mg/kg daily. Group III (maximum therapeutic dose): rats were givenretinylpalmitate 100 mg/kg daily. The viable offspring of all groups were evaluated for changes in developing spinal cord at PND10. At the end of the experiment, rats offspring were sacrificed, the spinal cord were dissected out, and subjected to histological examination followed by computer image analysis. Results PDN10 neonates of mothers received minimum dose of vitamin A (subgroup II) revealed few immature irregular dorsal horn neurons with relatively decreased cellular density in anterior horn neurons. Meanwhile, the PDN10 neonates of mothers received daily maximum therapeutic dose of vitamin A (subgroup III) exhibited dark,pyknotic nucleiand packed dorsal horn cells while anterior horn cells were shrunkenandkaryoliticnuclei. Conclusion minimum and maximum doses of vitamin A in pregnant rats attributed to morphological changes in spinal cord of their young neonates and in long term follow up which was more obvious in maximum dose than low intake. Therefore, it might be assumed that neither minimum nor maximum dose could be used as a safe drug for their serious side effects on spinal cord morphology and consequently its functions.

Sustained experimental activation of FGF8/ERK in the developing chicken spinal cord reproducibly models early events in ERK-mediated tumorigenesis

Most human cancers demonstrate activated MAPK/ERK pathway signaling as a key tumor initiation step, but the immediate steps of further oncogenic progression are poorly understood due to a lack of appropriate models. Spinal cord differentiation follows caudal elongation in vertebrate embryos; both processes are regulated by a FGF8 gradient highest in neuromesodermal progenitors (NMP), where kinase effectors ERK1/2 maintain an undifferentiated state. FGF8/ERK signal attenuation is necessary for NMPs to progress to differentiation. We show that sustained ERK1/2 activity, using a constitutively active form of the kinase MEK1 (MEK1ca) in the chicken embryo, reproducibly provokes neopasia in the developing spinal cord. Transcriptomic data show that neoplasia not only relies on the maintenance of NMP gene expression, and the inhibition of genes expressed in the differentiating spinal cord, but also on a profound change in the transcriptional signature of the spinal cord cells leading to a complete loss of cell-type identity. MEK1ca expression in the developing spinal cord of the chicken embryo is therefore a tractable in vivo model to identify the critical factors fostering malignancy in ERK-induced tumorigenesis.

Sulfation of Glycosaminoglycans Modulates the Cell Cycle of Embryonic Mouse Spinal Cord Neural Stem Cells

In the developing spinal cord neural stem and progenitor cells (NSPCs) secrete and are surrounded by extracellular matrix (ECM) molecules that influence their lineage decisions. The chondroitin sulfate proteoglycan (CSPG) DSD-1-PG is an isoform of receptor protein tyrosine phosphatase-beta/zeta (RPTPβ/ζ), a trans-membrane receptor expressed by NSPCs. The chondroitin sulfate glycosaminoglycan chains are sulfated at distinct positions by sulfotransferases, thereby generating the distinct DSD-1-epitope that is recognized by the monoclonal antibody (mAb) 473HD. We detected the epitope, the critical enzymes and RPTPβ/ζ in the developing spinal cord. To obtain insight into potential biological functions, we exposed spinal cord NSPCs to sodium chlorate. The reagent suppresses the sulfation of glycosaminoglycans, thereby erasing any sulfation code expressed by the glycosaminoglycan polymers. When NSPCs were treated with chlorate and cultivated in the presence of FGF2, their proliferation rate was clearly reduced, while NSPCs exposed to EGF were less affected. Time-lapse video microscopy and subsequent single-cell tracking revealed that pedigrees of NSPCs cultivated with FGF2 were strongly disrupted when sulfation was suppressed. Furthermore, the NSPCs displayed a protracted cell cycle length. We conclude that the inhibition of sulfation with sodium chlorate interferes with the FGF2-dependent cell cycle progression in spinal cord NSPCs.

HoxD transcription factors define monosynaptic sensory-motor specificity in the developing spinal cord

The specificity of monosynaptic connections between proprioceptive sensory neurons and their recipient spinal motor neurons depends on multiple factors, including motor neuron positioning and dendrite morphology, axon projection patterns of proprioceptive sensory neurons in the spinal cord, and the ligand-receptor molecules involved in cell-to-cell recognition. However, with few exceptions, the transcription factors engaged in this process are poorly characterized. We show here, that members of the HoxD family of transcription factors play a critical role in the specificity of monosynaptic sensory-motor connections. Mice lacking Hoxd9, Hoxd10, and Hoxd11 exhibit defects in locomotion but have no obvious defects in motor neuron positioning or dendrite morphology through the medio-lateral and rostro-caudal axes. However, we found that quadriceps motor neurons in these mice show aberrant axon development and receive inappropriate inputs from proprioceptive sensory axons innervating the obturator muscle. These genetic studies demonstrate that the HoxD transcription factors play an integral role in the synaptic specificity of monosynaptic sensory-motor connections in the developing spinal cord.

Mutations in phospholipase C eta-1 (PLCH1) are associated with holoprosencephaly

BackgroundHoloprosencephaly is a spectrum of developmental disorder of the embryonic forebrain in which there is failed or incomplete separation of the prosencephalon into two cerebral hemispheres. To date, dominant mutations in sonic hedgehog (SHH) pathway genes are the predominant Mendelian causes, and have marked interfamilial and intrafamilial phenotypical variabilities.MethodsWe describe two families in which offspring had holoprosencephaly spectrum and homozygous predicted-deleterious variants in phospholipase C eta-1 (PLCH1). Immunocytochemistry was used to examine the expression pattern of PLCH1 in human embryos. We used SHH as a marker of developmental stage and of early embryonic anatomy.ResultsIn the first family, two siblings had congenital hydrocephalus, significant developmental delay and a monoventricle or fused thalami with a homozygous PLCH1 c.2065C>T, p.(Arg689*) variant. In the second family, two siblings had alobar holoprosencephaly and cyclopia with a homozygous PLCH1 c.4235delA, p.(Cys1079ValfsTer16) variant. All parents were healthy carriers, with no holoprosencephaly spectrum features. We found that the subcellular localisation of PLCH1 is cytoplasmic, but the p.(Cys1079ValfsTer16) variant was predominantly nuclear. Human embryo immunohistochemistry showed PLCH1 to be expressed in the notorcord, developing spinal cord (in a ventral to dorsal gradient), dorsal root ganglia, cerebellum and dermatomyosome, all tissues producing or responding to SHH. Furthermore, the embryonic subcellular localisation of PLCH1 was exclusively cytoplasmic, supporting protein mislocalisation contributing to the pathogenicity of the p.(Cys1079ValfsTer16) variant.ConclusionOur data support the contention that PLCH1 has a role in prenatal mammalian neurodevelopment, and deleterious variants cause a clinically variable holoprosencephaly spectrum phenotype.

Programmed Cell Senescence in the Mouse Developing Spinal Cord and Notochord

Programmed cell senescence is a cellular process that seems to contribute to embryo development, in addition to cell proliferation, migration, differentiation and programmed cell death, and has been observed in evolutionary distant organisms such as mammals, amphibians, birds and fish. Programmed cell senescence is a phenotype similar to stress-induced cellular senescence, characterized by the expression of the cell cycle inhibitors p21CIP1/WAF and p16INK4A, increased activity of a lysosomal enzyme with beta-galactosidase activity (coined senescence-associated beta-galactosidase) and secretion of growth factors, interleukins, chemokines, metalloproteases, etc., collectively known as a senescent-associated secretory phenotype that instructs surrounding tissue. How wide is the distribution of programmed cell senescence during mouse development and its specific mechanisms to shape the embryo are still poorly understood. Here, we investigated whether markers of programmed cell senescence are found in the developing mouse spinal cord and notochord. We found discrete areas and developmental windows with high senescence-associated beta galactosidase in both spinal cord and notochord, which was reduced in mice embryos developed ex-utero in the presence of the senolytic ABT-263. Expression of p21CIP1/WAF was documented in epithelial cells of the spinal cord and the notochord, while p16INK4A was observed in motoneurons. Treatment with the senolytic ABT-263 decreased the number of motoneurons, supporting their senescent phenotype. Our data suggest that a subpopulation of motoneurons in the developing spinal cord, as well as some notochord cells undergo programmed cell senescence.

HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of Lzts1

ABSTRACTDifferential Hox gene expression is central for specification of axial neuronal diversity in the spinal cord. Here, we uncover an additional function of Hox proteins in the developing spinal cord, restricted to B cluster Hox genes. We found that members of the HoxB cluster are expressed in the trunk neural tube of chicken embryo earlier than Hox from the other clusters, with poor antero-posterior axial specificity and with overlapping expression in the intermediate zone (IZ). Gain-of-function experiments of HoxB4, HoxB8 and HoxB9, respectively, representative of anterior, central and posterior HoxB genes, resulted in ectopic progenitor cells in the mantle zone. The search for HoxB8 downstream targets in the early neural tube identified the leucine zipper tumor suppressor 1 gene (Lzts1), the expression of which is also activated by HoxB4 and HoxB9. Gain- and loss-of-function experiments showed that Lzts1, which is expressed endogenously in the IZ, controls neuronal delamination. These data collectively indicate that HoxB genes have a generic function in the developing spinal cord, controlling the expression of Lzts1 and neuronal delamination.