TY - JOUR
T1 - The development of the human notochord
AU - de Bree, Karel
AU - de Bakker, Bernadette S.
AU - Oostra, Roelof-Jan
PY - 2018
Y1 - 2018
N2 - The notochord is a major regulator of embryonic patterning in vertebrates and abnormal notochordal development is associated with a variety of birth defects in man. Proper knowledge of the development of the human notochord, therefore, is important to understand the pathogenesis of these birth defects. Textbook descriptions vary significantly and seem to be derived from both human and animal data whereas the lack of references hampers verification of the presented data. Therefore, a verifiable and comprehensive description of the development of the human notochord is needed. Our analysis and three-dimensional (3D) reconstructions of 27 sectioned human embryos ranging from Carnegie Stage 8 to 15 (17-41 days of development), resulted in a comprehensive and verifiable new model of notochordal development. Subsequent to gastrulation, a transient group of cells briefly persists as the notochordal process which is incorporated into the endodermal roof of the gut while its dorsal side attaches to the developing neural tube. Then, the notochordal process embeds entirely into the endoderm, forming the epithelial notochordal plate, which remains intimately associated with the neural tube. Subsequently, the notochordal cells detach from the endoderm to form the definitive notochord, allowing the paired dorsal aortae to fuse between the notochord and the gut. We show that the formation of the notochordal process and plate proceeds in cranio-caudal direction. Moreover, in contrast to descriptions in the modern textbooks, we report that the formation of the definitive notochord in humans starts in the middle of the embryo, and proceeds in both cranial and caudal directions.
AB - The notochord is a major regulator of embryonic patterning in vertebrates and abnormal notochordal development is associated with a variety of birth defects in man. Proper knowledge of the development of the human notochord, therefore, is important to understand the pathogenesis of these birth defects. Textbook descriptions vary significantly and seem to be derived from both human and animal data whereas the lack of references hampers verification of the presented data. Therefore, a verifiable and comprehensive description of the development of the human notochord is needed. Our analysis and three-dimensional (3D) reconstructions of 27 sectioned human embryos ranging from Carnegie Stage 8 to 15 (17-41 days of development), resulted in a comprehensive and verifiable new model of notochordal development. Subsequent to gastrulation, a transient group of cells briefly persists as the notochordal process which is incorporated into the endodermal roof of the gut while its dorsal side attaches to the developing neural tube. Then, the notochordal process embeds entirely into the endoderm, forming the epithelial notochordal plate, which remains intimately associated with the neural tube. Subsequently, the notochordal cells detach from the endoderm to form the definitive notochord, allowing the paired dorsal aortae to fuse between the notochord and the gut. We show that the formation of the notochordal process and plate proceeds in cranio-caudal direction. Moreover, in contrast to descriptions in the modern textbooks, we report that the formation of the definitive notochord in humans starts in the middle of the embryo, and proceeds in both cranial and caudal directions.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85055158799&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30346967
U2 - https://doi.org/10.1371/journal.pone.0205752
DO - https://doi.org/10.1371/journal.pone.0205752
M3 - Article
C2 - 30346967
SN - 1932-6203
VL - 13
JO - PLOS ONE
JF - PLOS ONE
IS - 10
M1 - e0205752
ER -