Scientists from the University of Barcelona (UB) in collaboration with a multidisciplinary team from the Spanish National Research Council (CSIC) has discovered a mechanism that prevents alterations in neurogenesis, the process of neuronal formation, during the development of the nervous system in vertebrates. The study, published in the journal Development, relates these distortions to the natural presence of a molecule that inhibits the neuronal formation at the regions adjacent to the tissue suitable for neurogenesis.
Through a theoretical and computational analysis of the retina, scientists have found that lateral inhibition, a process that regulates the generation of neurons in the central nervous system, undergoes alterations at the neurogenic wavefront (i.e. the edge between the regions that generate neurons and the adjacent areas, where neurogenesis has not yet begun).
"The study shows that the absence of the Delta molecule at the adjacent regions reduces the robustness of the neurogenic process, often resulting in an increased production of neurons or in the presence of morphological alterations of the wavefront. These alterations could be catastrophic for the proper development of the nervous system," explains Jos้ Marํa Frade, researcher from the CSIC, at the Cajal Institute.
Lateral inhibition during embryonic development aims to control the amount of neurons that are formed. It consists in cells that inhibit other neighbouring cells, promoting neuronal differentiation. "Neuronal precursor cells expressing high levels of Delta induce inhibitory signals in neighbouring cells. These inhibitory signals reduce the capacity of these cells to express Delta itself and, in turn, facilitate the differentiation of the high Delta-expressing precursors. Thus, the massive generation of neurons is avoided and the orderly production of different types of neurons necessary for brain function is facilitated," explains researcher from the CSIC Sa๚l Ares, who works at the Spanish National Biotechnology Centre.
Previous theoretical studies suggested that the lateral inhibition process can be altered at the neurogenic edges. "However, the importance of this inhibition process had not been appropriately acknowledged. Our study demonstrates the relevance of Delta expression ahead of the neurogenic wavefront, provides predictions and explains developmental alterations resulting from the absence of Delta. It also represents a breakthrough in the theoretical field because it formulates a front propagation mechanism based on self-regulatory mechanisms," points out Marta Iba๑es, researcher from the UB.
According to researchers, this study provides a new concept that will attract the attention of neurobiologists who work both in the development of the nervous system and in several pathologies derived from neuronal development.
- P. Formosa-Jordan, M. Ibanes, S. Ares, J. M. Frade. Regulation of neuronal differentiation at the neurogenic wavefront. Development, 2012; 139 (13): 2321 DOI: 10.1242/dev.076406
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