Traction forces exerted by the developing optic cup mediate cell movements and axon extension in the olfactory placode

While the chemical signals guiding neuronal migration and axon elongation have been extensively studied, the influence of mechanical cues on these processes remains poorly studied in vivo. Here, we investigate how mechanical forces exerted by surrounding tissues steer neuronal movements and axon extension during the morphogenesis of the olfactory placode in zebrafish. We mainly focus on the mechanical contribution of the adjacent eye tissue, which develops underneath the placode through extensive evagination and invagination movements. Using quantitative analysis of cell movements and biomechanical manipulations, we show that the developing eye exerts lateral traction forces on the olfactory placode through extracellular matrix, mediating proper morphogenetic movements and axon extension within the placode. Our data shed new light on the key participation of intertissue mechanical interactions in the sculpting of neuronal circuits.

Dissecting the neural divide: A continuous neurectoderm gives rise to both the olfactory placode and olfactory bulb

The olfactory epithelia arise from morphologically identifiable structures called olfactory placodes. Sensory placodes are generally described as being induced from the ectoderm suggesting that their development is separate from the coordinated cell movements generating the central nervous system. Previously, we have shown that the olfactory placodes arise from a large field of cells bordering the telencephalic precursors in the neural plate, and that cell movements, not cell division, underlie olfactory placode morphogenesis. Subsequently by image analysis, cells were tracked as they moved in the continuous sheet of neurectoderm giving rise to the peripheral (olfactory organs) and central (olfactory bulbs) nervous system (Torres-Paz and Whitlock, 2014). These studies lead to a model whereby the olfactory epithelia develop from within the border of the neural late and are a neural tube derivative, similar to the retina of the eye (Torres-Paz and Whitlock, 2014; Whitlock, 2008). Here we show that randomly generated clones of cells extend across the morphologically differentiated olfactory placodes/olfactory bulbs, and test the hypothesis that these structures are patterned by a different level of distal-less (dlx) gene expression subdividing the anterior neurectoderm into OP precursors (high Dlx expression) and OB precursors (lower Dlx expression). Manipulation of DLX protein and RNA levels resulted in morphological changes in the size of the olfactory epithelia and olfactory bulb. Thus, the olfactory epithelia and bulbs arise from a common neurectodermal region and develop in concert through coordinated morphological movements.

Haploinsufficiency of Homeodomain Proteins Six3, Vax1, and Otx2 Causes Subfertility in Mice via Distinct Mechanisms

Haploinsufficiency occurs when loss of one copy of a diploid gene (hemizygosity) causes a phenotype. It is relatively rare, in that most genes can produce sufficient mRNA and protein from a single copy to prevent any loss of normal activity and function. Reproduction is a complex process relying on migration of GnRH neurons from the olfactory placode to the hypothalamus during development. We have studied 3 different homeodomain genes Otx2, Vax1, and Six3 and found that the deletion of one allele for any of these genes in mice produces subfertility or infertility in one or both sexes, despite the presence of one intact allele. All 3 heterozygous mice have reduced numbers of GnRH neurons, but the mechanisms of subfertility differ significantly. This review compares the subfertility phenotypes and their mechanisms.

Cell-type heterogeneity in the zebrafish olfactory placode is generated from progenitors within preplacodal ectoderm

Vertebrate olfactory placodes consists of a variety of neuronal populations, which are thought to have distinct embryonic origins. In the zebrafish, while ciliated sensory neurons arise from preplacodal ectoderm (PPE), previous lineage tracing studies suggest that both Gonadotropin releasing hormone 3 (Gnrh3) and microvillous sensory neurons derive from cranial neural crest (CNC). We find that the expression of Islet1/2 is restricted to Gnrh3 neurons associated with the olfactory placode. Unexpectedly, however, we find no change in Islet1/2+ cell numbers in sox10 mutant embryos, calling into question their CNC origin. Lineage reconstruction based on backtracking in time-lapse confocal datasets, and confirmed by photoconversion experiments, reveals that Gnrh3 neurons derive from the anterior/medial PPE. Similarly, all of the microvillous sensory neurons we have traced arise from preplacodal progenitors. Our results suggest that rather than originating from separate ectodermal populations, cell-type heterogeneity is generated from overlapping pools of progenitors within the preplacodal ectoderm.