The growth of the human brain during the embryonic period proper

Summary Linear axes of the brain were measured in 143 human embryos from Carnegie stages 11 to 23 (3 1/2–8 postovulatory weeks). The embryos ranged from 3 to 30 mm in C.-R. length. Both Born reconstructions and serial sections of the central nervous system were used. The brain axes included were the fronto-occipital diameter, bitemporal diameter, and length and width of both the mesencephalon and cerebellum. A least squares line was fitted to the set of data points corresponding to each brain axis measured, and a t test verified that a linear model was an appropriate representation of the data. Based on these linear measurements it can be concluded that the forebrain grows more rapidly than the rest of the brain at the onset of tubular brain enlargement. Furthermore, as seen by comparing growth along two dimensions, the forebrain and midbrain grow at the same rate, whereas the cerebellum grows at different rates along the length and height axes. In addition, the cerebellum begins to grow later than the rostral part of the brain. Covariance analysis of the data points of the embryonic brain axes with data points of identical brain axes of the fetus showed that the measurements from the embryonic and fetal brain axes cannot be represented by a single regression line.Supported by research programme project grant No. HD-08658, Institute of Child Health and Human Development, National Institutes of Health (U.S.A.)     

Ventricular system and choroid plexuses of the human brain during the embryonic period proper

This morphological study, based on serial sections and graphic reconstructions at 4–8 postovulatory weeks (stages 11–23), is believed to be the first account of the ventricular system in staged human embryos. Closure of the caudal neuropore at stage 12 heralds the onset of the ventricular system and separates the ependymal from the amniotic fluid. After the appearance of the optic ventricle at stage 11, the cavity of the telencephalon medium is discernible at stage 13. At stage 14 the future cerebral hemispheres and lateral ventricles begin, and the rhomboid fossa becomes apparent. The medial and lateral ventricular eminences cause indentations in the lateral ventricle by stage 15. The hypothalamic sulcus is evident at stage 16. At stages 17–18 the interventricular foramina are becoming relatively smaller, and cellular accumulations indicate the future choroid villi of the fourth and lateral ventricies. The areae membranaceae rostralis and caudalis are visible in the roof of the fourth ventricle at state 18, and the paraphysis is appearing. At stage 19 choroid villi are seen in the fourth ventricle, and a mesencephalic evagination (Blindsack) is detectable. Choroid villi are noticeable in the lateral ventricle at state 20. An olfactory ventricle is present by stage 21. At about stages 21–23 the lateral ventricle has become C -shaped, so that anterior and inferior horns are visible. Several recesses, e.g., the optic, infundibular, and pineal, develop in the third ventricle during the embryonic period. Features of the ventricular system that do not become apparent until the fetal period include the posterior horn of the lateral ventricle, choroid plexus of the third ventricle, suprapineal recess, interthalamic adhesion, aqueduct, and apertures in the roof of the fourth ventricle.     

The timing and sequence of events in the development of the human nervous system during the embryonic period proper

Summary A documented scheme of the early development of the human nervous system is presented. It is based on (I) reports of workers who personally studied staged embryos, and (2) personal observations and confirmations. The necessity of staged embryos in determining the precise sequence of developmental events is stressed.Supported in part by National Institutes of Health (U.S.A.) General Research Support Grant, School of Medicine, Wayne State University.     

The timing and sequence of events in the development of the human urinary system during the embryonic period proper

Summary A documented scheme of the early development of the human urinary system is presented. It is based on (1) reports of workers who personally studied staged embryos, and (2) personal observations and confirmations. The necessity of studying staged embryos in order to determine the precise sequence of developmental events is stressed.Supported in part by National Institutes of Health (U.S.A.) General Research Support Grant, School of Medicine, Wayne State University.     

The timing and sequence of events in the development of the human respiratory system during the embryonic period proper

Summary A documented scheme of the early development of the human respiratory system is presented. It is based on (1) reports of workers who personally studied staged embryos, and (2) personal observations and confirmations. The necessity of studying staged embryos in order to determine the precise sequence of developmental events is stressed.     

The timing and sequence of events in the development of the human vertebral column during the embryonic period proper

Summary A documented scheme of the early development of the human vertebrae is presented. It is based on (1) reports of workers who personally studied staged human embryos, and (2) personal observations and confirmations. The necessity of studying staged embryos in order to determine the precise sequence of developmental events is stressed.Supported by research programme project grant No. HD-08658, Institute of Child Health and Human Development, National Institutes of Health (U.S.A.)     

The timing and sequence of events in the development of the human digestive system and associated structures during the embryonic period proper

Summary A documented scheme of the early development of the human digestive system is presented. It is based on (1) reports of workers who personally studied staged embryos, and (2) personal observations and confirmations. The necessity of studying staged embryos in order to determine the precise sequence of developmental events is stressed.Supported by research programme project grant No. HD-08658, Institute of Child Health and Human Development, National Institutes of Health (U.S.A.)     

Cardiomyogenesis in the embryonic period of human development

The morphological analysis of major processes involved in cardiac myogenesis (including cytodifferentiation, proliferation, integration and apoptosis) was carried out by studying the myocardium of 52 human embryos at weeks 4 to 8 of development. The data provided by this study, permit to draw a conclusion on the coupling of high proliferative activity of cardiomyocytes, their active divergent differentiation, formation of the integrative intercellular communications and manifestations of programmed cell death relations during this period of ontogenesis. Starting with week 6 of intrauterine life, the developing atrial and ventricular cardiac muscular tissue demonstrates the heteromorphy of constituting cardiomyocytes, which differentiate into three types: contractile, contractile-secretory and conducting ("light").     

The human lung during the embryonic period: vasculogenesis and primitive erythroblasts circulation

Vascularization and blood cell circulation are crucial steps during lung development. However, how blood vessels are generated and when lung circulation is initiated is still a matter of debate. A morpho‐functional analysis of pulmonary vasculature was done using human lung samples between 31 and 56 days post‐fertilization (pf). The immunolocalization and expression of CD31, CD34, FLT‐1, KDR and the vascular growth factor (VEGF) were investigated. The results showed that at day 31 pf, a capillary plexus is already installed, and a few primitive erythroblasts were seen for the first time within the lumen of some blood vessels. Around day 45 pf, an increase in the amount of primitive erythroblasts was detected in the parenchyma surrounding the distal segment of the bronchial tree. The expression of FLT‐1, KDR, CD31 and CD34 was observed in endothelial cells of the capillary plexus and the VEGF was detected in the endodermal epithelium. Our results support the hypothesis that the initial formation of the capillary plexus around the tip of the growing airway bud occurs by vasculogenesis, probably regulated by VEGF and KDR. We also showed a very early onset of blood circulation, starting from day 34 pf, concomitant with the generation of new lung buds. In addition, the increasing number of primitive erythroblasts from week 6 onward, associated with a change in the shape of the blood vessels, suggests a remodeling process and that the generation of new distal vessels at the tip of the lung bud occurs mainly by a process of angiogenesis.     

The development of the tensor vastus intermedius during the human embryonic period and its clinical implications

The tensor vastus intermedius (TVI) is a newly discovered muscle located in the anterolateral thigh area and is considered the fifth component of the quadriceps femoris muscle. There have been several papers describing its anatomical and morphological features in detail; however, many features of this muscle, such as its ontology or kinetic functions, remain unknown. The purpose of this study was to determine the initial appearance of the TVI muscle in human embryonic development and to investigate its growth and development. Histological observations were performed on 30 lower limbs of 15 human embryos from Carnegie stage (CS) 21, 22, and 23 (with crown-rump length ranging from 18.7 to 28.7 mm). Myocyte clusters of the TVI were observed between the vastus lateralis and intermedius muscles in 7 out of 10 limbs in CS 22, indicating that the TVI arises during this stage. In CS 23, the TVI was clearly present in all specimens except one. However, neither the aponeurosis nor the tendonous structure of the TVI were observed in these embryonic stages. Formation of the conventional four components of the quadriceps muscle is completed within CS 21; therefore, our results suggest that the TVI is the last element to develop in the quadriceps femoris complex. It is posited that after the embryonic period, the TVI continues to grow, while forming the tendinous structure toward the patella and receiving vascular supply from certain vascular branches. The clinical significance of these findings is that orthopedists and plastic surgeons who perform surgical procedures within the anterolateral thigh (ALT) area should be aware of the anatomy and development of the TVI in order to reduce surgical complications. Our present research aims to contribute to a deeper understanding of the morphogenesis of the TVI and the other femoral extensor muscles.     

Development and morphogenesis of human wrist joint during embryonic and early fetal period

The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O'Rahilly stages 17-23 and 9-14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology.     

Starting at the end

From the time when I entered immunology - in January 1965 at the Salk Institute for Biological Studies in La Jolla, California in the laboratories of Edwin (Ed) Lennox and Melvin (Mel) Cohn - my love has always been B lymphocytes and antibodies. I began my studies at the end of the developmental pathway of these B cells, with plasma cells. After more than 40 years in immunology, I have moved "backwards" over mature B cells, immature B cells, precursor B cells and lymphocyte progenitors to pluripotent hematopoietic stem cells. Initially it was an intellectual exercise to trace the unknown progenitor of known B-lineage cells; now it has become an experimental approach - to de- and re-differentiate B-lineage cells to earlier differentiation stages and to other lineages of hematopoietic cells.