Morphogenesis is transcriptionally coupled to neurogenesis during peripheral olfactory organ development

Abstract

Sense organs acquire their distinctive shapes concomitantly with the differentiation of sensory cells and neurons necessary for their function. While our understanding of the mechanisms controlling morphogenesis and neurogenesis in these structures has grown, how these processes are coordinated remains largely unexplored. Neurogenesis in the zebrafish olfactory epithelium requires the bHLH proneural transcription factor Neurogenin1 (Neurog1). To address whether Neurog1 also controls morphogenesis in this system, we analysed the morphogenetic behaviour of early olfactory neural progenitors in neurog1 mutant embryos. Our results indicate that the oriented movements of these progenitors are disrupted in this context. Morphogenesis is similarly affected by mutations in the chemokine receptor gene,cxcr4b, suggesting it is a potential Neurog1 target gene. We find that Neurog1 directly regulates cxcr4b through an E-boxes cluster located just upstream of the cxcr4b transcription start site. Our results suggest that proneural transcription factors, such as Neurog1, directly couple distinct aspects of nervous system development.

Intertissue mechanical interactions shape the olfactory circuit in zebrafish

“…Conversely, the lateral movements were decreased in eyeless rx3 -/mutants, but we did not detect significant defects in anteroposterior convergence movements, although the anteroposterior OP dimension was increased at the end of OP coalescence (24s). This increase could be due to a weak perturbation of Cxcl12a/Cxcr4b signaling in rx3 -/mutants, consistent with the previously described posterior expansion of the telencephalon (Stigloher et al, 2006;Bielen, Houart, 2012), known to express the Cxcl12a ligand (Miyasaka et al, 2007;Aguillon et al, 2020).…”

“…We initially hypothesized that cells from the anterior and posterior extremities of the OP—while actively converging—may compress the central cells, thereby squeezing them away from the brain and contributing to the elongation of their axons (Breau et al , 2017). To test this, we ablated the cells that would exert this compression, using the Tg(‐8.4neurog1:GFP) line (Blader et al , 2003) referred to below as the ngn1:gfp line, which labels the early‐born neurons in the OP (Madelaine et al , 2011; Breau et al , 2017; Aguillon et al , 2020). In practice, we laser ablated 10–20 ngn1:gfp + cells in both anterior and posterior extremities of one placode when convergence occurs, at 14–16s (the placode typically comprising a hundred ngn1:gfp + cells at this stage (Breau et al , 2017)), the contralateral placode serving as a control (Fig 1B and C).…”

“…In the embryo, the placodes assemble through the coalescence of progenitors located in large domains of the pan‐placodal region (Breau & Schneider‐Maunoury, 2014, 2015), while or soon before initiating axonal contacts with the brain (Zecca et al , 2015; Breau et al , 2017). During their assembly, neurogenic placodes are surrounded by several non‐placodal tissues undergoing morphogenetic reorganization, including the brain (Torres‐Paz & Whitlock, 2014; Breau et al , 2017; Aguillon et al , 2020), the optic cup (Kwan et al , 2012) and neural crest cells (Harden et al , 2012; Torres‐Paz & Whitlock, 2014). The superficial location of the zebrafish neurogenic placodes, right underneath the epidermis, facilitates live imaging of cell dynamics and biomechanical manipulations.…”

“…Our study focuses on the morphogenesis of the olfactory placode (OP), which later gives rise to the olfactory epithelium. OP cells are initially located in two elongated domains next to the brain, which both coalesce into paired ellipsoidal neuronal clusters over 7 h of development, between 14 and 21 h post‐fertilization (hpf) (corresponding to 12 somites (12s) and 24s stages) (Whitlock & Westerfield, 2000; Harden et al , 2012; Breau et al , 2017; Aguillon et al , 2020). We previously showed that OP coalescence is driven by two types of cell movements (Breau et al , 2017) (Fig 1A).…”

“…Remarkably, axon growth initiates during lateral movements through retrograde extension, whereby cell bodies move away from their axon tips attached to the brain (Breau et al , 2017) (Fig 1A). While the anteroposterior active convergence is guided by Cxcr4b/Cxcl12a signalling downstream of the transcription factor Neurogenin1 (Miyasaka et al , 2007; Aguillon et al , 2020), the mechanisms driving the lateral phase of OP cell movements, during which axons elongate, remain elusive. We previously proposed that the lateral displacement of the cell bodies is a passive, non‐autonomous process, based on the following findings: (i) the lack of protrusive activity and of polarized actin and myosin II in the laterally moving cell bodies, (ii) the absence of lateral movement defects upon inhibition of microtubule polymerization or upon cell autonomous perturbation of actomyosin activity, and (iii) the lack of lateral movement defects when we disrupted the axons or their attachment to the brain (Breau et al , 2017).…”