Molecular and morphogenetic features of neurulation

Authors

DOI:

https://doi.org/10.14739/2310-1210.2024.1.288912

Keywords:

neurulation, neural tube defects, neural tube

Abstract

Neurulation occurs by two different mechanisms, called primary and secondary neurulation. In humans, primary neurulation occurs along most of the rostrocaudal axis of the embryo, while secondary neurulation occurs caudally, only in the lower sacral and coccygeal regions. Primary neurulation is responsible for a change in the neural plate shape, the lateral edges of which rise and then converge at the dorsal midline to merge into a tube. Initially, the neural tube, formed as a result of primary neurulation, is open at both ends through the so-called rostral and caudal neuropores. These neuropores connect the inner part of the neural tube with the environment (amniotic cavity) and later (by the end of primary neurulation) are closed. During primary neurulation, the brain and spinal cord are formed up to the upper sacral region (up to the level of junction between S1 and S2 vertebral bodies), however, the most caudal part of this anatomical region (sacral-coccygeal division of the spinal cord, conus medullaris and filum terminale) is formed at secondary neurulation. In humans, secondary neurulation occurs due to elongation and cavitation of the caudal cell mass into the medulla, which then transforms into a secondary neural tube.

Thus, the main differences between primary and secondary neurulation are that the neural plate folds and invaginates into the body of the embryo and separates from the surface ectoderm, forming an underlying hollow tube in primary neurulation. Mesenchymal cell сlusters form a dense cord that undergoes mesenchymal-epithelial transition and forms cavities and an empty tube during secondary neurulation to form the terminal part of the spinal cord.

Conclusions. Understanding the detailed molecular and genetic mechanisms of each stage of neurulation is relevant due to widespread congenital neural tube defects, and only perfect knowledge on each aspect of neurulation and all possible factors of potential influence on it will help to develop modern options for influencing some of them, and probably, cause a decrease in neural tube congenital defects.

Author Biographies

N. M. Nevmerzhytska, Bogomolets National Medical University, Kyiv, Ukraine

Assistant of the Department of Histology and Embryology

O. M. Grabovyi, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, DSc, Professor, Acting Head of the Department of Histology and Embryology

L. M. Yaremenko, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, DSc, Professor of the Department of Histology and Embryology

I. V. Dzevulska, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Descriptive and Clinical Anatomy

A. M. Synytska, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, Associate Professor of the Department of Descriptive and Clinical Anatomy

H. I. Kozak, Bogomolets National Medical University, Kyiv, Ukraine

MD, PhD, Associate Professor of the Department of Histology and Embryology

References

Benavides-Rivas C, Tovar LM, Zúñiga N, Pinto-Borguero I, Retamal C, Yévenes GE, et al. Altered Glutaminase 1 Activity During Neurulation and Its Potential Implications in Neural Tube Defects. Front Pharmacol. 2020;11:900. doi: https://doi.org/10.3389/fphar.2020.00900

Tovar LM, Burgos CF, Yévenes GE, Moraga-Cid G, Fuentealba J, Coddou C, et al. Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation. Int J Mol Sci. 2023;24(3):2159. doi: https://doi.org/10.3390/ijms24032159

Murphy SL, Xu J, Kochanek KD, Arias E. Mortality in the United States, 2017. NCHS Data Brief. 2018;(328):1-8.

Baldwin AT, Kim JH, Seo H, Wallingford JB. Global analysis of cell behavior and protein dynamics reveals region-specific roles for Shroom3 and N-cadherin during neural tube closure. Elife. 2022;11:e66704. doi: https://doi.org/10.7554/eLife.66704

Yadav JK, Khizar A, Yadav PK, Mustafa G, Bhatti SN. A case report of triple neural tube defect: revisiting the multisite closure theory. BMC Surg. 2019;19(1):164. doi: https://doi.org/10.1186/s12893-019-0633-2

Abdel Fattah AR, Daza B, Rustandi G, Berrocal-Rubio MÁ, Gorissen B, Poovathingal S, et al. Actuation enhances patterning in human neural tube organoids. Nat Commun. 2021;12(1):3192. doi: https://doi.org/10.1038/s41467-021-22952-0

Wang M, Marco P, Capra V, Kibar Z. Update on the Role of the Non-Canonical Wnt/Planar Cell Polarity Pathway in Neural Tube Defects. Cells. 2019;8(10):1198. doi: https://doi.org/10.3390/cells8101198

de Goederen V, Vetter R, McDole K, Iber D. Hinge point emergence in mammalian spinal neurulation. Proc Natl Acad Sci U S A. 2022;119(20):e2117075119. doi: https://doi.org/10.1073/pnas.2117075119

Kim KH, Lee JY, Wang KC. Secondary Neurulation Defects-1 : Retained Medullary Cord. J Korean Neurosurg Soc. 2020;63(3):314-20. doi: https://doi.org/10.3340/jkns.2020.0052

Catala M. Overview of Secondary Neurulation. J Korean Neurosurg Soc. 2021;64(3):346-58. doi: https://doi.org/10.3340/jkns.2020.0362

Bueno D, Parvas M, Nabiuni M, Miyan J. Embryonic cerebrospinal fluid formation and regulation. Semin Cell Dev Biol. 2020;102:3-12. doi: https://doi.org/10.1016/j.semcdb.2019.09.006

Fedorova V, Vanova T, Elrefae L, Pospisil J, Petrasova M, Kolajova V, et al. Differentiation of neural rosettes from human pluripotent stem cells in vitro is sequentially regulated on a molecular level and accomplished by the mechanism reminiscent of secondary neurulation. Stem Cell Res. 2019;40:101563. doi: https://doi.org/10.1016/j.scr.2019.101563

Darnell D, Gilbert SF. Neuroembryology. Wiley Interdiscip Rev Dev Biol. 2017;6(1):10.1002/wdev.215. doi: https://doi.org/10.1002/wdev.215

Ko HY. Neural Tube Defects and Abnormalities in Neurulation. In: Management and Rehabilitation of Spinal Cord Injuries. Singapore: Springer Nature Singapore; 2022. p. 371-9. doi: https://doi.org/10.1007/978-981-19-0228-4_18

Choi S, Kim KH, Kim SK, Wang KC, Lee JY. Three-dimensional visualization of secondary neurulation in chick embryos using microCT. Dev Dyn. 2022;251(5):885-96. doi: https://doi.org/10.1002/dvdy.441

Wang KC. Perspectives : The Role of Clinicians in Understanding Secondary Neurulation. J Korean Neurosurg Soc. 2021;64(3):414-7. doi: https://doi.org/10.3340/jkns.2021.0040

Wu Y, Peng S, Finnell RH, Zheng Y. Organoids as a new model system to study neural tube defects. FASEB J. 2021;35(4):e21545. doi: https://doi.org/10.1096/fj.202002348R

Zhang L, Wei X. Stepwise modulation of apical orientational cell adhesions for vertebrate neurulation. Biol Rev Camb Philos Soc. 2023;98(6):2271-83. doi: https://doi.org/10.1111/brv.13006

Ravi KS, Divasha, Hassan SB, Pasi R, Mittra S, Kumar R. Neural tube defects: Different types and brief review of neurulation process and its clinical implication. J Family Med Prim Care. 2021;10(12):4383-90. doi: https://doi.org/10.4103/jfmpc.jfmpc_904_21

Williams RM, Lukoseviciute M, Sauka-Spengler T, Bronner ME. Single-cell atlas of early chick development reveals gradual segregation of neural crest lineage from the neural plate border during neurulation. Elife. 2022;11:e74464. doi: https://doi.org/10.7554/eLife.74464

van der Spuy M, Wang JX, Kociszewska D, White MD. The cellular dynamics of neural tube formation. Biochem Soc Trans. 2023;51(1):343-52. doi: https://doi.org/10.1042/BST20220871

Lavalou J, Lecuit T. In search of conserved principles of planar cell polarization. Curr Opin Genet Dev. 2022;72:69-81. doi: https://doi.org/10.1016/j.gde.2021.11.001

Shi DL. Wnt/planar cell polarity signaling controls morphogenetic movements of gastrulation and neural tube closure. Cell Mol Life Sci. 2022;79(12):586. doi: https://doi.org/10.1007/s00018-022-04620-8

Matsuda M, Rozman J, Ostvar S, Kasza KE, Sokol SY. Mechanical control of neural plate folding by apical domain alteration. Nat Commun. 2023;14(1):8475. doi: https://doi.org/10.1038/s41467-023-43973-x

Sulistomo HW, Nemoto T, Yanagita T, Takeya R. Formin homology 2 domain-containing 3 (Fhod3) controls neural plate morphogenesis in mouse cranial neurulation by regulating multidirectional apical constriction. J Biol Chem. 2019;294(8):2924-34. doi: https://doi.org/10.1074/jbc.RA118.005471

Roellig D, Theis S, Proag A, Allio G, Bénazéraf B, Gros J, et al. Force-generating apoptotic cells orchestrate avian neural tube bending. Dev Cell. 2022;57(6):707-18.e6. doi: https://doi.org/10.1016/j.devcel.2022.02.020

Nikolopoulou E, Hirst CS, Galea G, Venturini C, Moulding D, Marshall AR, et al. Spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2. Nat Commun. 2019;10(1):2487. doi: https://doi.org/10.1038/s41467-019-10164-6

De Castro SCP, Hirst CS, Savery D, Rolo A, Lickert H, Andersen B, et al. Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues. Dev Biol. 2018;435(2):130-7. doi: https://doi.org/10.1016/j.ydbio.2018.01.016

Nikolopoulou E, Galea GL, Rolo A, Greene ND, Copp AJ. Neural tube closure: cellular, molecular and biomechanical mechanisms. Development. 2017;144(4):552-66. doi: https://doi.org/10.1242/dev.145904

Kim KH, Lee JY. Junctional Neurulation : A Junction between Primary and Secondary Neural Tubes. J Korean Neurosurg Soc. 2021;64(3):374-9. doi: https://doi.org/10.3340/jkns.2021.0021

Eibach S, Pang D. Junctional Neural Tube Defect. J Korean Neurosurg Soc. 2020;63(3):327-37. doi: https://doi.org/10.3340/jkns.2020.0018

Lesko AC, Keller R, Chen P, Sutherland A. Scribble mutation disrupts convergent extension and apical constriction during mammalian neural tube closure. Dev Biol. 2021;478:59-75. doi: https://doi.org/10.1016/j.ydbio.2021.05.013

Yu J, Wang L, Pei P, Li X, Wu J, Qiu Z, et al. Reduced H3K27me3 leads to abnormal Hox gene expression in neural tube defects. Epigenetics Chromatin. 2019;12(1):76. doi: https://doi.org/10.1186/s13072-019-0318-1

Fame RM, Lehtinen MK. Mitochondria in Early Forebrain Development: From Neurulation to Mid-Corticogenesis. Front Cell Dev Biol. 2021;9:780207. doi: https://doi.org/10.3389/fcell.2021.780207

Keuls RA, Kojima K, Lozzi B, Steele JW, Chen Q, Gross SS, et al. MiR-302 Regulates Glycolysis to Control Cell-Cycle during Neural Tube Closure. Int J Mol Sci. 2020;21(20):7534. doi: https://doi.org/10.3390/ijms21207534

Steele JW, Kim SE, Finnell RH. One-carbon metabolism and folate transporter genes: Do they factor prominently in the genetic etiology of neural tube defects? Biochimie. 2020;173:27-32. doi: https://doi.org/10.1016/j.biochi.2020.02.005

Kim J, Lei Y, Guo J, Kim SE, Wlodarczyk BJ, Cabrera RM, et al. Formate rescues neural tube defects caused by mutations in Slc25a32. Proc Natl Acad Sci U S A. 2018;115(18):4690-5. doi: https://doi.org/10.1073/pnas.1800138115

Wolujewicz P, Ross ME. The search for genetic determinants of human neural tube defects. Curr Opin Pediatr. 2019;31(6):739-46. doi: https://doi.org/10.1097/MOP.0000000000000817

Findley TO, Tenpenny JC, O'Byrne MR, Morrison AC, Hixson JE, Northrup H, et al. Mutations in folate transporter genes and risk for human myelomeningocele. Am J Med Genet A. 2017;173(11):2973-84. doi: https://doi.org/10.1002/ajmg.a.38472

Cai CQ, Fang YL, Shu JB, Zhao LS, Zhang RP, Cao LR, et al. Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway. Ital J Pediatr. 2019;45(1):37. doi: https://doi.org/10.1186/s13052-019-0630-1

Lemay P, De Marco P, Traverso M, Merello E, Dionne-Laporte A, Spiegelman D, et al. Whole exome sequencing identifies novel predisposing genes in neural tube defects. Mol Genet Genomic Med. 2019;7(1):e00467. doi: https://doi.org/10.1002/mgg3.467

Zhang H, Guo Y, Gu H, Wei X, Ma W, Liu D, et al. TRIM4 is associated with neural tube defects based on genome-wide DNA methylation analysis. Clin Epigenetics. 2019;11(1):17. doi: https://doi.org/10.1186/s13148-018-0603-z

Kim SE, Lei Y, Hwang SH, Wlodarczyk BJ, Mukhopadhyay S, Shaw GM, et al. Dominant negative GPR161 rare variants are risk factors of human spina bifida. Hum Mol Genet. 2019;28(2):200-8. doi: https://doi.org/10.1093/hmg/ddy339

Sequerra EB, Goyal R, Castro PA, Levin JB, Borodinsky LN. NMDA Receptor Signaling Is Important for Neural Tube Formation and for Preventing Antiepileptic Drug-Induced Neural Tube Defects. J Neurosci. 2018;38(20):4762-73. doi: https://doi.org/10.1523/JNEUROSCI.2634-17.2018

Li B, Brusman L, Dahlka J, Niswander LA. TMEM132A ensures mouse caudal neural tube closure and regulates integrin-based mesodermal migration. Development. 2022;149(17):dev200442. doi: https://doi.org/10.1242/dev.200442

Chau KF, Shannon ML, Fame RM, Fonseca E, Mullan H, Johnson MB, et al. Downregulation of ribosome biogenesis during early forebrain development. Elife. 2018;7:e36998. doi: https://doi.org/10.7554/eLife.36998

Published

2024-02-05

How to Cite

1.
Nevmerzhytska NM, Grabovyi OM, Yaremenko LM, Dzevulska IV, Synytska AM, Kozak HI. Molecular and morphogenetic features of neurulation. Zaporozhye Medical Journal [Internet]. 2024Feb.5 [cited 2024Jun.30];26(1):72-7. Available from: http://zmj.zsmu.edu.ua/article/view/288912