Morphology, molecular phenotypes and distribution of neurons in developing human corpus callosum

Abstract

The aim of this study was to investigate the morphology, molecular phenotypes, distribution and developmental history of interstitial neurons in the human corpus callosum, here defined as intracallosal neurons. We analysed 26 fetuses, three newborns, five infants and children, and eight adults [age range - 15 weeks postconception (PCW) to 59 years] by means of acetylcholinesterase (AChE) histochemistry and immunohistochemistry for neuron markers (MAP2, NeuN, NPY, calretinin and calbindin). We found a heterogeneous neuron population, positioned within the callosal trunk itself (aside from neurons present in the transient midline structures such as callosal sling, septa or subcallosal zone), which was most numerous during the second half of gestation and early postnatal years. We named these cells intracallosal neurons. At 15 PCW, the intracallosal neuron population consisted of poorly differentiated, small fusiform or bipolar, migratory-like MAP2- or calretinin-positive neurons which could be observed until mid-gestation. Later the population comprised morphologically diverse, predominantly well-differentiated MAP2-, NPY-, calbindin- and AChE-positive neurons. The morphological differentiation of intracallosal neurons culminated in the newborns and remained pronounced in infants and children. In the adult brain, the intracallosal neurons were found only sporadically, with small somata and poorly stained dendrites. Thus, intracallosal neurons form part of a transitory neuron population with a developmental peak contemporaneous to the critical period of callosal formation. Therefore, they may be involved in processes such as axon guiding or elongation, withdrawal of exuberant axons, fasciculation, or functional tuning, which occur at that time.

Association of Type I Neurons Positive for NADPH-Diaphorase with Blood Vessels in the Adult Monkey Corpus Callosum

“…This may be related to the dorso-ventrally oriented septa described in the developing human callosum (Jovanov-Miloševic et al, 2010). These have been reported as transient modules; but some indication of what might be comparable septa in the adult macaque can be detected in our PV material (Figure 6).…”

“…In cats, the number drops from about 570 at birth to 200 in the adult, and the distribution becomes restricted to the rostrum (Riederer et al, 2004). In humans, what were called “intracallosal” neurons are most numerous in the second half of gestation and the early postnatal years, but are found only sporadically in the adult brain (Jovanov-Miloševic et al, 2010). In our adult monkey material, NADPHd+ neurons were sparsely distributed, but readily identified.…”

The Ciliogenic Transcription Factor RFX3 Regulates Early Midline Distribution of Guidepost Neurons Required for Corpus Callosum Development

“…More recently, GABAergic (γ-aminobutyric acidergic) neurons and glutamatergic neurons that populate transiently the CSB have also been shown to be involved in guiding callosal axons at the midline [11]. These glial and neuronal guidepost populations are also observed in the human foetal CC [2], [12].…”

Neuronal Migration of Guidepost Cells

“…Its absence is associated with an acallosal phenotype, that can be rescued by a 'sling graft,' supporting a major role for this structure in the guidance of callosal axons Katz et al, 1983;Shu and Richards, 2001;Silver and Ogawa, 1983;Silver et al, 1982Silver et al, , 1993. While, the presence of neurons in the corpus callosum was reported in the cat, mouse, and human (Jovanov-Milosevic et al, 2010;Ren et al, 2006;Riederer and Innocenti, 1992;Riederer et al, 2004), recent studies have revealed that the 'glial' sling is largely composed of glutamatergic immature neurons expressing NeuN, b-tubulin, calretinin, Emx1, and NFIA (Niquille et al, 2009;Ren et al, 2006;Shu et al, 2003b). They are generated from E14.5 to P2 and have been proposed to migrate medially from the ventricular zone next to the sling (Figure 25.5; Niquille et al, 2009;Shu et al, 2003b) or from retrobulbar regions (Meyer and Goffinet, 1998;.…”