Int. J. Dev. Biol. 57: 341 - 350 (2013)

https://doi.org/10.1387/ijdb.120259jf

Vol 57, Issue 5

Lateral inhibition and neurogenesis: novel aspects in motion

Review | Published: 9 July 2013

Pau Formosa-Jordan¹, Marta Ibañes¹, Saúl Ares^2,3 and José-María Frade*^,4

¹Department of Estructura i Constituents de la Matèria, Facultat de Física, Universitat de Barcelona, Barcelona, ²Logic of Genomic Systems Laboratory, ³Grupo Interdisciplinar de Sistemas Complejos (GISC), Spanish National Biotechnology Centre CNB-CSIC, Madrid and ⁴Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, IC-CSIC, Madrid, Spain.

Abstract

Neuronal production in metazoans is tightly controlled by Delta/Notch-dependent signals regulating lateral inhibition. It is currently thought that lateral inhibition takes place in clusters of precursors with equal capacity to trigger and receive Notch-dependent inhibitory signals. However, this view neglects crucial dynamical aspects of the process. In this review, we discuss two of these dynamic factors, whose alterations yield dysfunctions in neurogenesis. First, precursors show variable neurogenic capacity as they go through the cell cycle. Second, differentiating precursors are in direct contact with non-neurogenic cells at the wavefront of expanding neurogenic domains. We discuss the mechanisms adopted by Metazoa to prevent these dysfunctions in the lateral inhibitory process, which include cell cycle synchronization occurring in the invertebrate neural epithelium and during primary neurogenesis in anamniotes, interkinetic nuclear movement in the vertebrate neuroepithelium and generalized Delta expression ahead of the neurogenic wavefront. The emerging concept is that lateral inhibition during neurogenesis occurs in dynamic clusters of precursors and requires specific mechanisms to avoid distortions resulting from the interaction between neurogenic and non-neurogenic precursors. The advance in visualizing Notch dynamics with real-time imaging at cellular and subcellular levels will notably contribute to our understanding of these novel “aspects of motion” in neurogenesis.

Keywords

notch, delta, cell cycle, interkinetic nuclear movement, neurogenic wavefront