Lateral inhibition and neurogenesis: novel aspects in motion

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.

RasGRF2 controls nuclear migration in postnatal retinal cone photoreceptors

“…Correct nuclear positioning is known to be essential for adequate function of a wide range of cells and organisms from yeast to mammals (Dupin and Etienne-Manneville, 2011). In vertebrate neuroepithelia, the nuclei of precursor cells undergo movements along the apicobasal axis in a process called interkinetic nuclear migration (INM) that is synchronized with their cell cycle and cell fate determination mechanisms, thus giving rise to pseudostratified epithelia (Formosa-Jordan et al, 2013;Latasa et al, 2009). INM is also essential for correct development of precursor cells and stratified layers in the vertebrate retina during embryonal development (Bassett and Wallace, 2012;Cepko et al, 1996;Del Bene et al, 2008), but the mechanisms of cone nuclear movement, occurring postnatally in a process called the late migratory phase (Rich et al, 1997), are still poorly understood.…”

Neurogenic gene regulatory pathways in the sea urchin embryo

“…Furthermore, when DeltaNotch signaling is blocked by treatment with DAPT, which is a gamma secretase inhibitor of Notch signaling, SoxC-expressing cells increase in number and form small clusters (Fig. 1F), reflecting the loss of lateral inhibition that is also characteristic of neural precursors (Formosa-Jordan et al, 2013). The number and positions of SoxC-expressing cells varied among embryos at the same time of development (Fig.…”

Regulation of downstream neuronal genes by proneural transcription factors during initial neurogenesis in the vertebrate brain

“…This patterning is regulated in part by the Notch signalling pathway, which has remained highly conserved throughout vertebrate evolution. Lateral inhibition with feedback regulation allows Notch signalling to maintain the number of neural progenitor cells (NPCs) by controlling the number of neighbouring cells that can exit the cell cycle and subsequently undergo neural differentiation [14]. Cell cycle exit is controlled by a limited number of basic helix-loop-helix (bHLH) proneural genes that are both necessary and sufficient to activate neurogenesis [5, 28].…”