22Cell migration requires dynamic regulation of cell-cell signaling and cell adhesion. Neural crest (NC) cells 23 are highly migratory cells, which undergo an epithelial-mesenchymal transition (EMT) to leave the neural 24 epithelium and migrate throughout the body to give rise to many different derivatives. We have identified 25 a Lim-domain only (Lmo) protein, Lmo7a, expressed in early NC cells that controls both actin cytoskeletal 26 dynamics and Wnt signaling during NC migration. In embryos deficient in Lmo7a, many NC cells fail to 27 migrate away from the dorsal midline, and form aggregates. Unlike the majority of NC cells that appear to 28 migrate normally, cells that aggregate in Lmo7a-deficient embryos mislocalize paxillin (Pxn) and have 29 reduced levels of phosphorylated focal adhesion kinase (pFAK). Lmo7a loss-of-function also disrupts 30canonical Wnt signaling such that after the onset of NC cell migration, Wnt responses and nuclear β-31 catenin levels increase in the cells that aggregate. However, this increase in Wnt signaling appears 32 secondary to the defect in migration. Similar to mutants for other Wnt regulators in NC cells, the NC cells 33in Lmo7a-deficient aggregates exhibit gene expression signatures of pigment cell progenitors, but also 34 express markers of Schwann cell progenitors, suggesting a role for Lmo7a in pigment-glial specification. 35We propose that Lmo7a modulates cell adhesion to facilitate both robust NC cell migration and a subset 36 of lineage decisions.
1Vertebrate olfactory placodes consists of a variety of neuronal populations, which are 2 thought to have distinct embryonic origins. In the zebrafish, while ciliated sensory 3 neurons arise from preplacodal ectoderm (PPE), previous lineage tracing studies 4 suggest that both Gonadotropin releasing hormone 3 (Gnrh3) and microvillous 5 sensory neurons derive from cranial neural crest (CNC). We find that the expression 6 of Islet1/2 is restricted to Gnrh3 neurons associated with the olfactory placode. 7Unexpectedly, however, we find no change in Islet1/2+ cell numbers in sox10 mutant 8 embryos, calling into question their CNC origin. Lineage reconstruction based on 9 backtracking in time-lapse confocal datasets, and confirmed by photoconversion 10 experiments, reveals that Gnrh3 neurons derive from the anterior/medial PPE. 11Similarly, all of the microvillous sensory neurons we have traced arise from 12 preplacodal progenitors. Our results suggest that rather than originating from 13 separate ectodermal populations, cell-type heterogeneity is generated from 14 overlapping pools of progenitors within the preplacodal ectoderm. 15 16. CC-BY 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/194175 doi: bioRxiv preprint first posted online Sep. 26, 2017; 3 Introduction 1 A fundamental question in developmental neurobiology is how different neuronal 2 subtypes arise from fields of pluripotent progenitors. At the end of gastrulation, the 3 anterior neural plate border of vertebrate embryos gives rise to two specialized 4 regions of ectoderm: the preplacodal ectoderm (PPE) that will ultimately produce the 5 cranial placodes, and the cranial neural crest (CNC). Specification of the PPE is 6 achieved through the action of so-called preplacodal competence factors such as 7 tfap2a, tfap2c, foxi1 and gata3 (Kwon et al., 2010). During a similar time-window, key 8 neural crest specifier genes, such as foxd3 (Lister et al., 2006; Montero-Balaguer et 9 al., 2006; Stewart et al., 2006), tfap2a (Barrallo-Gimeno et al., 2004) 2016)). Concomitantly, CNC cells delaminate and migrate throughout the head, 16where they have been reported to contribute to a large number of cell types, 17 including neurons associated with derivatives of the cranial placodes. These include 18 sensory neurons of the various peripheral sensory ganglia (D'Amico-Martel and 19 Noden, 1983; Harlow and Barlow, 2007), as well as sensory and neurosecretory cells 20 of the olfactory system (Whitlock et al., 2003; Saxena et al., 2013). This dual 21 embryonic (PPE/CNC) origin for olfactory neurons may have critical developmental 22 and functional consequences. 23In zebrafish embryos, olfactory neurons are generated in two waves, early 24 olfactory neurons (EON) and olfactory sensory neurons (OSN), under the redundant 25 control of the bHLH proneural transcr...
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