Imaging, anatomical, and molecular analysis of callosal formation in the developing human fetal brain

Abstract

A complex set of axonal guidance mechanisms are utilized by axons to locate and innervate their targets. In the developing mouse forebrain, we previously described several midline glial populations as well as various guidance molecules that regulate the formation of the corpus callosum. Since agenesis of the corpus callosum is associated with over 50 different human congenital syndromes, we wanted to investigate whether these same mechanisms also operate during human callosal development. Here we analyze midline glial and commissural development in human fetal brains ranging from 13 to 20 weeks of gestation using both diffusion tensor magnetic resonance imaging and immunohistochemistry. Through our combined radiological and histological studies, we demonstrate the morphological development of multiple forebrain commissures/decussations, including the corpus callosum, anterior commissure, hippocampal commissure, and the optic chiasm. Histological analyses demonstrated that all the midline glial populations previously described in mouse, as well as structures analogous to the subcallosal sling and cingulate pioneering axons, that mediate callosal axon guidance in mouse, are also present during human brain development. Finally, by Northern blot analysis, we have identified that molecules involved in mouse callosal development, including Slit, Robo, Netrin1, DCC, Nfia, Emx1,, are all expressed in human fetal brain. These data suggest that similar mechanisms and molecules required for midline commissure formation operate during both mouse and human brain development. Thus, the mouse is an excellent model system for studying normal and pathological commissural formation in human brain development.

Variability of Homotopic and Heterotopic Callosal Connectivity in Partial Agenesis of the Corpus Callosum: A 3T Diffusion Tensor Imaging and Q-Ball Tractography Study

“…However, some recent studies propose a more complex callosal development pattern, in which growth is initiated simultaneously at 2 distinct loci: a rostral locus at the lamina rostralis and a more caudal locus above the hippocampal commissure. [32][33][34] Disruption of growth in this more complex model could account for the anatomic diversity of callosal fragments seen in our cohort. However, the observation of varying connectivity even between subjects with morphologically similar callosal fragments, including diverse patterns of heterotopic connectivity, suggests that a more plastic and complex mechanism is at work.…”

Mild Hypoxic-Ischemic Injury in the Neonatal Rat Brain: Longitudinal Evaluation of White Matter Using Diffusion Tensor MR Imaging

“…It has been proposed that during maturation, increase of longitudinally oriented neurofibrils and the elevation of fast axonal transport 15 increase water diffusion along axons, which increases // . However, axonal pruning reduces intermingling axon branches and shortens the length of axons, 32,33 which decreases // . Therefore, longitudinal changes of // may not be significant.…”

Disorders of prosencephalic development

“…There has been some debate about the timing of the development of the rostrum, the small frontal Copyright  2009 John Wiley & Sons, Ltd. part of the CC. Whereas clinical observation appears to agree that this should be the last portion to develop, recent studies based on diffusion tensor magnetic resonance imaging were able to demonstrate that the rostrum together with the genu and the anterior part of the body were already present at around 15 weeks (Ren et al, 2006).…”