Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC27610.15690/vramn.v67i8.348PROCEEDINGS OF THE RAMS SESSIONМАТЕРИАЛЫ СЕССИИ РАМНTHE EARLY EMBRYONAL ANOMALIES OF HUMAN BRAINПАТОЛОГИЯ ЭМБРИОНАЛЬНОГО МОРФОГЕНЕЗА ГОЛОВНОГО МОЗГА ЧЕЛОВЕКАSavel'evS. V.СавельевС. В.
Russian Federation

доктор биологических наук, профессор, руководитель лаборатории развития нервной системы НИИ морфологии человека РАМН Адрес: 117418, Москва, ул. Цюрупы, д. 3 Тел.: (499) 120-00-50

braincase@yandex.ruInstitute of Human morphology Russian academy of medical scienceФГБУ «Научно-исследовательский институт морфологии человека» РАМН, Москва11082012678Вестник Российской академии медицинских наук404607082015Copyright ©; 2012, "Paediatrician" Publishers LLCCopyright ©; 2012, Издательство "Педиатръ"2012"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/article/view/276

The mechanisms of early embryonic pathology of the brain in man and animals were studied. Analysis of the biomechanical properties of development of nervous tissue and embryonal experiments demonstrated that tangential neuroepithelial intention is the major source of positional information. Experimental changes in the neuroepithelial intention system resulted in various types of embryonal anomalies of the nervous system. Mechanical-dependent ion channels that have marked periods of sensitivity and determine the histogenetic direction of neuroblast cell differentiation were found to underline the mechanosensitivity of the neuroepithelium. Experimental findings were compared with unique autopsy data on early development of the human brain. Human embryos were examined from neurulation to month 6 of development. Different types of human embryonal brain anomalies were shown to occur with 3 types of neurulation disordes: 1) an open preneuropore is responsible for anomalies of the forebrain and etmoidal area; 2) arrested neurulation in the postneuropore leads to anomalies of the diencephalons, midbrain, and occipital region; 3) impaired neurulatuion in the caudal region is a cause of spinal cord anomalies. The above anomalies resulted from local compensatory responses of the neuroepithelium due to the lack of intentions that are characteristic of normal development of the neural tube.

Исследованы механизмы развития ранней эмбриональной патологии нервной системы у человека и экспериментальных животных. Установлены биомеханические принципы кодирования позиционной информации нейроэпителиальными клетками. Экспериментальное обратимое изменение тангенциальных межклеточных взаимодействий в нейроэпителии животных приводило к прогнозируемым аномалиям развития нервной системы. Изменение проницаемости механозависимых ионных каналов является основным способом считывания позиционной информации и детерминации клеточной дифференцировки. Было проведено сравнение экспериментальных аномалий мозга у животных с уникальными аутопсиями патологического развития мозга человека начиная от нейруляции и заканчивая 6-м мес внутриутробного развития. Полученные результаты позволили установить, что при задержке движения постнейропорной волны замыкания нервной трубки формируются аномалии переднего мозга и этмоидной части лица. Обнаружено, что при остановке движения постнейропорной волны нейруляции формируются аномалии промежуточного и среднего мозга, а при нарушении каудальной волны — аномалии заднего и спинного мозга. Показано, что аномалии развития, диагностируемые на поздних сроках онтогенеза и после рождения, являются последствиями компенсаторных реакций нейроэпителия на изменение ранних позиционных сигналов в период формирования нервной трубки.

brain developmentneurulationanomaliesразвитие мозганейруляцияаномалии1. Savel'ev S.V. Neyrulyatsionnye forms of pathology of the nervous system of humans. Arkhiv patologii = Archives of Pathology. 1998; 5: 13–18.2. Hugehes A. Development of the primary sensory system in Xenopus laevis (Daudin). J. Anat. 1957; 91: 323–328.3. Tanaka D.J., Bursian S.J. Degneration patterns in the chicken central nervous system induced by ingestion of the organophosphorus delayed neurotoxin 3-orthototolylphosphate. A silver impregnation study. Brain Res. 1989; 484: 240–256.4. Simon EM, Barkovich AJ. Holoprosencephaly: new concepts. Magn. Reson. Imaging. Clin. N. Am. 2001; 9 (1): 149–164.5. Stockard C.R. Developmental rate and structural expression: An experimental study of twins, «double monsters» and single deformities, and the interaction among embryonic organs during their origin and development. Am. J. Anat. 1921; 28: 115–277.6. Savel'ev S.V. Biomechanics neuroepithelium vertebrates. Zhurn. Obshch. Biol. = Journal of general biology. 1993; 54: 72–80.7. Savel'ev S.V. Formoobrazovanie mozga pozvonochnykh [Shaping the brain of vertebrates]. Moscow, Iz-vo. MGU, 1993. p. 143.8. Savel'ev S.V. The mechanism of encoding positional information in the embryonic brain morphogenesis of vertebrates. Vestnik RAMN = Annals of RAMS. 2001; 4: 49–61.9. Savel'ev S.V. Abnormal development of the nervous system in the human embryo 3.2 mm in length. Morfologiya = Morphology. 1993; 104 (1–2): 25–33.10. Savel'ev S.V. Neurolitic forms of pathology of the nervous system of humans. Arkhiv patologii = Archives of Pathology. 1998; 5: 13–18.11. Savel'ev S.V., Besova N.V., Istomin A.A. Mekhanozavisimye anomalii rannego embrional'nogo formoobrazovaniya golovnogo mozga cheloveka. V sb.: Aktual'nye voprosy sovremennoi gistopatologii [Mehanozavisimye anomalies early embryonic morphogenesis of the human brain. Proc .: Actual problems of modern histopathology]. Moscow, IMCh RAMN, 1989. 112 p.12. Belintsev B.N., Belousov L.V., Zaraiskii A.G. Model epithelial morphogenesis based on elastic forces and the contact cell polarization. I. Ontogenez = Ontogeny. 1985; 16 (1): 5–14.13. Savel'ev S.V. Role of polarization and cell migration in the embryonic brain morphogenesis amphibians. Ontogenez = Ontogeny. 1987; 18 (4): 360–368.14. Savel'ev S.V. Analysis of the formation of the brain in Siberian salamander embryos. Ontogenez = Ontogeny. 1987; 18 (6): 639–650.15. Muller F., O’Rahilly R. The first appearance of the major divisions of the human brain at stage 9. Anat. Embryol. 1983; 168: 419–432.16. Muller F., O’Rahilly R. Cerebral dysraphia (future anencephaly) in a guman twin embryo at stage 13. Teratology. 1984; 30: 167–177.17. O’Rahilly R., Muller F., Hutchins G.M. et al. Computer ranking of the sequence of appearance of 73 features of the brain and related structures in staged human embryos during the sixth week of development. Am. J. Anat. 1987; 180: 69–86.18. Vermeij-Keers Chr., Mazzola R.F., Van der Meulen J.C. et al. Cerebro-craniofacial and craniofacial malformations: An embryological analysis. Cleft Palate J. 1983; 20: 128–145.19. Savel'ev S.V. Embrional'naya patologiya nervnoi sistemy [Fetal pathology of the nervous system]. Moscow, Vedi, 2007. p. 215.20. Savel'ev S.V. Stadii embrional'nogo razvitiya mozga cheloveka [Stages of embryonic development of the human brain.]. Moscow, Vedi, 2002. p. 109.21. Lemire R.J. Neural tube defects: Clinical correlations. In Proceedings of The congress of neurological surgeons. Toronto. Williams, Wilkins, Baltimore. 1982. 165–177.22. Fraser F.C., Czeizel A., Hanson C. Increased frequency of neural tube defects in sibs of children with other malformations. Lancet. 1982; 2: 144–145.23. Patten B.M. Embryological stages in the establishing of myeloschisis with spina bifida. Am. J. Anat. 1953; 93: 365–395.24. Savel'ev S.V., Besova N.V. Polarization of neuroepithelial cells when administered portion of the neural plate into the cavity of the neural tube amphibian embryos. Ontogenez = Ontogeny. 1990; 21 (3): 298–303.25. Savel'ev S.V., Besova N.V. Morphogenetic effects of short-term tensile and compressive surface amphibian embryos at the blastula and gastrula. Ontogenez = Ontogeny. 1991; 226 (1): 30–38.26. Savel'ev S.V.,Chernikov V.P. Chernikov VP Morphogenesis of the human brain on the 27-35 th day of development in violation of neurulation. Izvestiya AN SSSR. Ser. Biol. = Proceedings of the USSR Academy of Sciences. Ser. Biology. 1992; 3: 465–471.27. Savel'ev S.V., Besova N.V.,Istomin A.A. Morphogenesis neuroepithelial layers of the human brain in terms of shaping. Morfologiya = Morphology.1992; 103: 32–41.28. Savel'ev S.V. Biomechanics neuroepithelium vertebrates. Zhurn. Obshch. Biol. = Journal of general biology. 1993; 54: 72–80.29. Savel'ev S.V. Neurolitic forms of pathology of the nervous system of humans. Arkhiv patologii = Archives of Pathology. 1998; 5: 13–18.30. Bell J.E. The pathology of central nervous system defects in human fetuses of different gestational ages. Adv. in the Study of Birth Defects. 1982. 1–17.31. Erskine C.A. Human anencephaly in early developmental stages. Acta Anat. 1965; 21: 251–258.32. Stoer W.F.H., van der Zwam A. Anencephaly and rhachischisis posterior with the description of a human hemicephalus of 18 mm. J. Anat. Lond. 1939; 73: 441–450.33. Probst F.P. The prosencephalies morphology, neuroradiological appearances and differential diagnosis. Berlin Springer. 1979; 35–65.34. Dodds G.S., De Angelis E. Anencephalic human embryo 16,5 mm long. Anat. Rec. 1937; 67: 499–505.35. Jacobson A.G. Further evidence that formation of the neural tube requires elongation of the nervous system. J. Exp. Zool. 1984; 230: 23–28.36. Jacobson A.G., Oster G.F., Odell G.M. Neurulation and the cortical tractor model for epithelial folding. J. Embryol. Exp. Morphol. 1986; 96: 19–49.37. Belintsev B.N., Belousov L.V., Zapaiskii A.G. Model-based epithelial morphogenesis of elastic contact forces and polarization of cells. II. Ontogenez = Ontogeny. 1985; 16 (5): 437–449.38. Belintsev B.N. Fizicheskie osnovy biologicheskogo formoobrazovaniya [Physical basis of biological pattern formation]. Moscow, Nauka, 1991. 252 p.39. Savel'ev S.V. Influence of the parietal meningoentsefalotselnoy hernia on morphogenesis of the human brain neuroepithelium. Izvestiya AN SSSR. Ser. Biol. = Proceedings of the USSR Academy of Sciences. Ser. Biology. 1991; 4: 633–639.40. Belousov L.V. Experiments to change fields axial tension rudiments of amphibian embryos. Ontogenez = Ontogeny. 1979;10 (2): 120–129.41. Belousov L.V. Mechanical stress as factors of autoregulation morphogenesis. Ontogenez = Ontogeny. 1989; 20 (6): 626–636.42. Savel'ev S.V. Some aspects of the formation of the brain in amphibian embryos. Ontogenez = Ontogeny. 1985; 16 (6): 620–627.43. Savel'ev S.V. Experimental study of mechanical stresses neuroepithelial layers of the brain. Ontogenez = Ontogeny. 1988; 19 (2): 165–174.44. Sachs F. Mechanical transduction in biological systems. Crit. Rev. Biomed. Eng. 1988; 16: 141–169.45. Morris C.E., Sigurdson W.J. Stretch-inactivated ion channels coexist with stretch-inactivated ion channels. Science. 1989; 243: 807–809.46. Spitzer N.C. A developmental handshake: Neuronal control of ionic currents and their control of neuronal differentiation. J. Neurobiol. 1991; 22: 659–673.47. Savel'ev S.V. Embryonic development mechanisms spina bifida in humans. Arkhiv patologii = Archives of Pathology. 2004; (2): 21–23.48. Corona-Rivera E. Holoprosencephaly, hypertelorism, and ectrodactyly in a boy with an apparently balanced de novo. Am. J. Med. Genet. 2000; 90 (5): 423–426.49. Padmanabhan R. Etiology, pathogenesis and prevention of neural tube defects. Congenital Anomalies. 2006; 46: 55–67.50. Savel'ev S.V. The mechanism of encoding positional information neuroepithelial cells in the brain of amphibian embryos. DAN SSSR – Reports of USSR Academy of Sciences. 1988; 301 (6): 1479–1483.51. Savel'ev S.V., Besova N.V. Integration mechanisms of early embryonic brain morphogenesis amphibians. Ontogenez = Ontogeny. 1988; 19 (5): 550–551.52. Savel'ev S.V., Besova N.V., Korochkin L.I. Influence of morphogenetic processes in gene expression during ontogenesis in Spanish newt. DAN SSSR = Reports of USSR Academy of Sciences. 1989; 305 (1): 215–218.53. Milovanov A.P., Savel'ev S.V. Vnutriutrobnoe razvitie cheloveka [Natal Development of a Person]. Moscow, MDV, 2006. 382 p.