Formation of Body Axes During Embryonic Development

Year 2023, Volume: 32 Issue: 4, 254 - 264, 31.12.2023

Gizem Kaya , Leman Sencar

https://doi.org/10.17827/aktd.1395539

Abstract

Different dynamic processes and numerous molecular mechanisms play a role in the body development process. Gastrulation, which occurs in the 3rd week of embryonic development, is the process of formation of the trilaminar germ disc from the bilaminar germ disc. Gastrulation is also a process that determines the formation of body axes. The formation of body axes is very important for embryonic development. Before and throughout gastrulation, the anteroposterior (AP), dorsoventral (DV) and left-right (LR) body axes are formed. There are two signaling centers in the mammalian embryo, one in the primitive node and the other in the anterior visceral endoderm (AVE). The primitive node expresses Nodal, Chordin, and Noggin, while the AVE expresses several genes (OTX2,LIM1, and HESX1) required for head formation. Nodal, a member of the TGF-β family, is the main regulator of primitive line and mesoderm formation and is very important for axis formation in embryonic development. The primitive streak expresses transcription factors and many specific genes. BMP, expressed by the primitive node, has an important role in the formation of the dorsal part of the body. Right-left asymmetry begins with cell-cell interactions that occur in the primitive node during gastrulation. Pitx 2, the transcription factor that is a major determinant of the left side, is strongly expressed on the left side. Another important genes on the left side are Lefty 1 and Lefty 2, which are members of the TGF-β family. In research to date, the genes that control the development of the right side of the embryo are not as well defined as those on the left side. In this review, how the body axes (anterior-posterior, dorsal-ventral and left-right) are formed during embryonic development and the signaling molecules involved in this development are explained.

Keywords

Gastrulation, axis formation, primitive streak, laterality

Embriyonik Gelişim Sırasında Vücut Eksenlerinin Oluşumu

Abstract

Farklı dinamik süreçler ve çok sayıda moleküler mekanizma vücut gelişim sürecinde rol oynamaktadır. Embriyonik gelişimin 3. haftasında gerçekleşen gastrulasyon bilaminar germ diskinden trilaminar germ diskin oluşma sürecidir. Gastrulasyon aynı zamanda vücut eksenlerinin oluşumunu belirleyen bir süreçtir. Vücut eksenlerinin oluşumu embriyonik gelişim için oldukça önemlidir. Gastrulasyon öncesinde ve gastrulasyon boyunca anteroposterior (AP), dorsoventral (DV) ve sol-sağ (LR) vücut eksenleri oluşur. Memeli embriyosunda biri primitif düğümde, diğeri anterior visseral endodermde (AVE) olmak üzere iki sinyal merkezi bulunmaktadır. Primitif düğüm Nodal, Chordin ve Noggin'i eksprese ederken, AVE ise baş oluşumu için gerekli olan çeşitli genleri (OTX2,LIM1 ve HESX1) eksprese eder. TGF-β ailesinin bir üyesi olan Nodal ise primitif çizgi ile mezoderm oluşumunun ana düzenleyicisidir ve embriyonik gelişimde eksen oluşumu için oldukça önemlidir. Primitif çizgi transkripsiyon faktörlerini ve çok sayıda spesifik geni ifade eder. Primitif düğüm tarafından eksprese olan BMP vücudun dorsal kısmının oluşumunda önemli role sahiptir. Sağ-sol asimetrisi gastrulasyon sırasında primitif düğümde gerçekleşen hücre-hücre etkileşimleri ile başlar. Sol tarafın ana belirleyicisi olan transkripsiyon faktörü olan Pitx 2, sol tarafta güçlü bir şekilde eksprese edilir. Sol taraftaki bir diğer önemli genler ise TGF-β ailesinin üyeleri olan Lefty 1 ve Lefty2'dir. Bugüne kadar yapılan araştırmalarda embriyonun sağ tarafının gelişimini kontrol eden genler sol tarafta olduğu kadar iyi tanımlanmamıştır. Bu derlemede, embriyonik gelişim sırasında vücut eksenlerinin (anterior-posterior ,dorsal-ventral ve sol-sağ) nasıl oluştuğu ve bu gelişimde yer alan sinyal molekülleri anlatılmıştır.

Keywords

Gatrulasyon, Eksen oluşumu, Primitif Çizgi, Lateralite

References

• Marikawa Y, Alarcon VB. Creation of trophectoderm, the first epithelium, in mouse preimplantation development. Results Probl Cell Differ. 2012;55:165-184.
• 2. Lu CC-w. The role of nodal signaling in anterior -posterior axis formation in the mouse embryo. Harvard University ProQuest Dissertations Publishing, Harvard University; 2004.
• 3. Brinster RL. Embryo development. J Anim Sci. May 1974;38(5):1003-1012.
• 4. Handyside AH, Hunter S. Cell division and death in the mouse blastocyst before implantation. Rouxs Arch Dev Biol. Oct 1986;195(8):519-526.
• 5. Marikawa Y, Alarcón VB. Establishment of trophectoderm and inner cell mass lineages in the mouse embryo. Mol Reprod Dev. Nov 2009;76(11):1019-1032.
• 6. Dean J. Oocyte-specific genes regulate follicle formation, fertility and early mouse development. J Reprod Immunol. Jan 2002;53(1-2):171-180.
• 7. Sadler TW. Langman's Medical Embryplogy. Vol 13: Wolters Kluwer Health; 2015.
• 8. Yamanaka Y, Ralston A, Stephenson RO, Rossant J. Cell and molecular regulation of the mouse blastocyst. Dev Dyn. Sep 2006;235(9):2301-2314.
• 9. Morris SA, Grewal S, Barrios F, et al. Dynamics of anterior-posterior axis formation in the developing mouse embryo. Nat Commun. Feb 14 2012;3:673.
• 10. Muhr J, Arbor TC, Ackerman KM. Embryology, Gastrulation. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023.
• 11. Beddington RS, Robertson EJ. Axis development and early asymmetry in mammals. Cell. Jan 22 1999;96(2):195-209.
• 12. Beddington RS. Induction of a second neural axis by the mouse node. Development. Mar 1994;120(3):613-620.
• 13. Aitana Perea-Gomez SMM. Chapter 10 - Formation of the Anterior-Posterior Axis in Mammals. Vol Second Edition2015.
• 14. SF G. Early Mammalian Development. Developmental Biology. 6 ed. Sunderland (MA)2000.
• 15. Montavon T, Soshnikova N. Hox gene regulation and timing in embryogenesis. Semin Cell Dev Biol. Oct 2014;34:76-84.
• 16. Rosenquist TA, Martin GR. Visceral endoderm-1 (VE-1): an antigen marker that distinguishes anterior from posterior embryonic visceral endoderm in the early post-implantation mouse embryo. Mech Dev. Jan 1995;49(1-2):117-121.
• 17. Stower MJ, Srinivas S. The Head's Tale: Anterior-Posterior Axis Formation in the Mouse Embryo. Curr Top Dev Biol. 2018;128:365-390.
• 18. Perea-Gomez A, Rhinn M, Ang SL. Role of the anterior visceral endoderm in restricting posterior signals in the mouse embryo. Int J Dev Biol. 2001;45(1):311-320.
• 19. Stower MJ, Srinivas S. Heading forwards: anterior visceral endoderm migration in patterning the mouse embryo. Philos Trans R Soc Lond B Biol Sci. Dec 5 2014;369(1657).
• 20. Srinivas S. Mammalian Embryo:Establishment of the Embryonic Axes. John Wiley & Sons. 2015.
• 21. Yamamoto M, Saijoh Y, Perea-Gomez A, et al. Nodal antagonists regulate formation of the anteroposterior axis of the mouse embryo. Nature. Mar 25 2004;428(6981):387-392.
• 22. Thomas PQ, Brown A, Beddington RS. Hex: a homeobox gene revealing peri-implantation asymmetry in the mouse embryo and an early transient marker of endothelial cell precursors. Development. Jan 1998;125(1):85-94.
• 23. Varlet I, Collignon J, Robertson EJ. nodal expression in the primitive endoderm is required for specification of the anterior axis during mouse gastrulation. Development. Mar 1997;124(5):1033-1044.
• 24. Mesnard D, Donnison M, Fuerer C, Pfeffer PL, Constam DB. The microenvironment patterns the pluripotent mouse epiblast through paracrine Furin and Pace4 proteolytic activities. Genes Dev. Sep 1 2011;25(17):1871-1880.
• 25. Petersen CP, Reddien PW. Wnt signaling and the polarity of the primary body axis. Cell. Dec 11 2009;139(6):1056-1068.
• 26. Kozmikova I, Kozmik Z. Wnt/β-catenin signaling is an evolutionarily conserved determinant of chordate dorsal organizer. Elife. May 26 2020;9.
• 27. Kumar V, Park S, Lee U, Kim J. The Organizer and Its Signaling in Embryonic Development. J Dev Biol. Nov 1 2021;9(4).
• 28. Andre P, Song H, Kim W, Kispert A, Yang Y. Wnt5a and Wnt11 regulate mammalian anterior-posterior axis elongation. Development. Apr 15 2015;142(8):1516-1527
• 29. Kimelman D, Martin BL. Anterior-posterior patterning in early development: three strategies. Wiley Interdiscip Rev Dev Biol. Mar-Apr 2012;1(2):253-266.
• 30. Huelsken J, Vogel R, Brinkmann V, Erdmann B, Birchmeier C, Birchmeier W. Requirement for beta-catenin in anterior-posterior axis formation in mice. J Cell Biol. Feb 7 2000;148(3):567-578.
• 31. Martinez-Barbera JP, Rodriguez TA, Beddington RS. The homeobox gene Hesx1 is required in the anterior neural ectoderm for normal forebrain formation. Dev Biol. Jul 15 2000;223(2):422-430.
• 32. T.W.Sadler. Lagnman's Medical Embryology. 13th ed. USA: Wolters Kluwer Health; 2020.
• 33. Bachiller D, Klingensmith J, Kemp C, et al. The organizer factors Chordin and Noggin are required for mouse forebrain development. Nature. Feb 10 2000;403(6770):658-661.
• 34. Dufort D, Schwartz L, Harpal K, Rossant J. The transcription factor HNF3beta is required in visceral endoderm for normal primitive streak morphogenesis. Development. Aug 1998;125(16):3015-3025.
• 35. Faial T, Bernardo AS, Mendjan S, et al. Brachyury and SMAD signalling collaboratively orchestrate distinct mesoderm and endoderm gene regulatory networks in differentiating human embryonic stem cells. Development. Jun 15 2015;142(12):2121-2135.
• 36. Yamaguchi TP, Takada S, Yoshikawa Y, Wu N, McMahon AP. T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification. Genes Dev. Dec 15 1999;13(24):3185-3190.
• 37. Fontanella F, van Maarle MC, Robles de Medina P, et al. Prenatal Evidence of Persistent Notochord and Absent Sacrum Caused by a Mutation in the T (Brachyury) Gene. Case Rep Obstet Gynecol. 2016;2016:7625341.
• 38. Postma AV, Alders M, Sylva M, et al. Mutations in the T (brachyury) gene cause a novel syndrome consisting of sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal. J Med Genet. Feb 2014;51(2):90-97.
• 39. Abas R, Masrudin SS, Harun AM, Omar NS. Gastrulation and Body Axes Formation: A Molecular Concept and Its Clinical Correlates. Malays J Med Sci. Dec 2022;29(6):6-14.
• 40. Levin M. Left-right asymmetry in embryonic development: a comprehensive review. Mech Dev. Jan 2005;122(1):3-25.
• 41. Hirokawa N, Tanaka Y, Okada Y, Takeda S. Nodal flow and the generation of left-right asymmetry. Cell. Apr 7 2006;125(1):33-45.
• 42. Burdine RD, Schier AF. Conserved and divergent mechanisms in left-right axis formation. Genes Dev. Apr 1 2000;14(7):763-776.
• 43. Carlson BM. Human Embryology and Devolopmental Biology. 6 ed. USA: Elsevier; 2019.
• 44. Nishimura Y, Kasahara K, Shiromizu T, Watanabe M, Inagaki M. Primary Cilia as Signaling Hubs in Health and Disease. Adv Sci (Weinh). Jan 9 2019;6(1):1801138.
• 45. Norris DP, Robertson EJ. Asymmetric and node-specific nodal expression patterns are controlled by two distinct cis-acting regulatory elements. Genes Dev. Jun 15 1999;13(12):1575-1588.
• 46. Belo JA, Marques S, Inácio JM. The Role of Cerl2 in the Establishment of Left-Right Asymmetries during Axis Formation and Heart Development. J Cardiovasc Dev Dis. Dec 10 2017;4(4)
• 47. Bataille S, Demoulin N, Devuyst O, et al. Association of PKD2 (polycystin 2) mutations with left-right laterality defects. Am J Kidney Dis. Sep 2011;58(3):456-460.
• 48. Langenbacher A, Chen JN. Calcium signaling: a common thread in vertebrate left-right axis development. Dev Dyn. Dec 2008;237(12):3491-3496.
• 49. Fukumoto T, Kema IP, Levin M. Serotonin signaling is a very early step in patterning of the left-right axis in chick and frog embryos. Curr Biol. May 10 2005;15(9):794-803.
• 50. Meyers EN, Martin GR. Differences in left-right axis pathways in mouse and chick: functions of FGF8 and SHH. Science. Jul 16 1999;285(5426):403-406.