Human-Rat Comparisons

Human-Rat Comparisons

Our developmental studies of the human central nervous system have been going on for close to 20 years.  At first, we used the monograph published in 1919 by Hochstetter to view various stages of human brain development, then matched them to rat brain development (see Figure 1 in Bayer et al. 1993; pdf file link below).  In the mid-90s, we went to Washington D.C. to study the human embryonic and fetal brains in the Carnegie, Minot, and Yakovlev Collections housed at the Armed Forces Institute of Pathology at Walter Reed Hospital.  Over 10,000 photos were taken of normal specimens from the time of closure of the neural tube into the early postnatal period.  The photos were digitized, and compiled into a large database of normal central nervous system development.  That work resulted in a large study of human spinal cord development (Altman, J. and S. A. Bayer [2001] Development of the Human Spinal Cord.  An  Interpretation Based on Experimental Studies in Animals.  New York, NY, Oxford University Press, see Our Books page) and a 5-volume series,  Atlas of Human Central Nervous System Development(see Our Books page for information) published between 2002 and 2007 by CRC Press/Taylor&Francis.  Essentially, we have been able to link our experimental findings of rat nervous system development to the human nervous system.  The illustrations below show just a few examples of the insights that we have gained from these studies.


 

The vertebrate neuroepithelium (NEP) is the primary germinal matrix of the central nervous system (CNS).  During the early embryonic development of the CNS, this distinctive tissue folds and then fuses to form the lining of the fluid-filled ventricles of the neural tube posteriorly and the brain vesicles anteriorly.  Initially, the NEP consists solely of stockbuilding, proliferating precursor cells of neurons and neuroglia.  Later during embryonic development, the differentiating neurons and neuroglia leave the NEP to form the specific structures of the spinal cord and brain.  The size of the NEP and the duration of its stockbuilding activity is a major factor in determining absolute and relative sizes of different brain regions.

The human neocortex, a principal organ of our intelligence, is distinguished in comparison with most other mammals not only by its large absolute volume but also by its large size relative to the hindbrain.  The above photos illustrate the early embryonic origins of that difference in rats and humans.  Initially, expansion of the neocortical NEP lags behind the midbrain/hindbrain NEPs but as the latter begin to shrink the neocortical NEP grows larger.  In RATS (right column), the neocortical NEP EXPANDS FOR ONLY 6 DAYS before young neurons start migrating into the cortical plate (the site that will differentiate into the cortical gray matter).  The expansion of the neocortical NEP relative to that of the midbrain and hindbrain is not pronounced.  In HUMANSTHE NEOCORTICAL NEP EXPANDS FOR SEVERAL WEEKS before the cortical plate emerges.  Recent studies suggest that the expansion of the neocortical NEP, the decline of the neocortical NEP, the migration of neurons into the cortical plate, and their phases of differentiation is regulated by a cascade of gene expression and transcription factors (Pax6, Emx1, Emx2, Otx2, Ngn1, Ngn2, and others).


 

The 9-week human embryo (approximately 63 days old) is 424% larger than the E18 rat embryo, but both embryos are near the same stage of development.  The basal ganglia, hypothalamus, midbrain, pons, medulla, and cerebellum are similar in both embryos.  However, the thalamus, and particularly the neuroepithelium of the cerebral cortex is much larger in the human than in the rat embryo.  In humans, the cortical neuroepithelium greatly expands over a “ballooning” lateral ventricle and a “blooming” choroid plexus and is the source of most neurons that will  populate the highly folded neocortex in the mature human brain.  By contrast in rats, the much smaller cortical neuroepithelium covers a more flat lateral ventricle with no blooming choroid plexuswhich leads to the production of many fewer neurons in the cerebral cortex of the mature rat brain.