Closure of the vertebral canal in human embryos and fetuses

Abstract

The vertebral column is the paradigm of the metameric architecture of the vertebrate body. Because the number of somites is a convenient parameter to stage early human embryos, we explored whether the closure of the vertebral canal could be used similarly for staging embryos between 7 and 10 weeks of development. Human embryos (5-10 weeks of development) were visualized using Amira 3D reconstruction and Cinema 4D remodelling software. Vertebral bodies were identifiable as loose mesenchymal structures between the dense mesenchymal intervertebral discs up to 6 weeks and then differentiated into cartilaginous structures in the 7th week. In this week, the dense mesenchymal neural processes also differentiated into cartilaginous structures. Transverse processes became identifiable at 6 weeks. The growth rate of all vertebral bodies was exponential and similar between 6 and 10 weeks, whereas the intervertebral discs hardly increased in size between 6 and 8 weeks and then followed vertebral growth between 8 and 10 weeks. The neural processes extended dorsolaterally (6th week), dorsally (7th week) and finally dorsomedially (8th and 9th weeks) to fuse at the midthoracic level at 9 weeks. From there, fusion extended cranially and caudally in the 10th week. Closure of the foramen magnum required the development of the supraoccipital bone as a craniomedial extension of the exoccipitals (neural processes of occipital vertebra 4), whereas a growth burst of sacral vertebra 1 delayed closure until 15 weeks. Both the cranial- and caudal-most vertebral bodies fused to form the basioccipital (occipital vertebrae 1-4) and sacrum (sacral vertebrae 1-5). In the sacrum, fusion of its so-called alar processes preceded that of the bodies by at least 6 weeks. In conclusion, the highly ordered and substantial changes in shape of the vertebral bodies leading to the formation of the vertebral canal make the development of the spine an excellent, continuous staging system for the (human) embryo between 6 and 10 weeks of development.

Shape analysis of the cervical spinous process

“…The developing mammalian neural tube initiates closure at several sites along its length, which roughly correspond to the cervical, thoracic, lumbar and sacral regions recognized in the adult vertebral column (Nakatsu et al, ). However, there is evidence that human embryological development may limit the initiation of closure to only the rostral and caudal ends of the tube (O'Rahilly and Muller, ; Mekonen et al, ). Failed closure of the neural tube can influence the development of the surrounding vertebrae and result in the condition that is generally known as spina bifida.…”

The development of the human notochord

“…Similar to gastrulation, the formation of the prechordal plate , notochordal process and -plate proceeds in craniocaudal direction. However, in contrast to the mechanism described in all modern textbooks, the formation of the definitive notochord including the initial notochordal plate's acquisition of an inverted U-shape, starts in the middle of the embryo, and then proceeds in both cranial and caudal directions, similar to the closure of the neural tube [ 32 ] and the subsequent formation of vertebral neural arches [ 33 ]. In contrast to the development of the notochord as illustrated in textbooks, the human notochord does not have a stage in which the process of gastrulation and the definitive notochord are simultaneously present, as can be observed for instance in chicken embryos [ 13 – 19 ] ( Fig 5 ).…”

Quantitative characteristic of vertebral tissues in human embryos and fetuses

“…В литературе для описания динамики роста линейных размеров/объема тела закладок позвонков и центров окостенения в них у плодов человека используются линейные [3,4], параболические [7], логарифмические [15] или экспоненциальные [16] функции. В проанализированной нами выборке установлено, что с возрастом увеличение высоты, поперечного и переднезаднего размеров тела закладок позвонков во всех отделах позвоночного столба носит линейный характер.…”

“…H.K. Mekonen et al [15] установили, что для этого параметра характерен экспоненциальный рост со скоростью ~6,5% в день.…”