During gastrulation, embryonic cells become specified into distinct germ layers. In mouse, this continues throughout somitogenesis from a population of bipotent stem cells called neuromesodermal progenitors (NMps). However, the degree of self-renewal associated with NMps in the fast-developing zebrafish embryo is unclear. Using a genetic clone-tracing method, we labelled early embryonic progenitors and found a strong clonal similarity between spinal cord and mesoderm tissues. We followed individual cell lineages using light-sheet imaging, revealing a common neuromesodermal lineage contribution to a subset of spinal cord tissue across the anterior-posterior body axis. An initial population subdivides at mid-gastrula stages and is directly allocated to neural and mesodermal compartments during gastrulation. A second population in the tailbud undergoes delayed allocation to contribute to the neural and mesodermal compartment only at late somitogenesis. Cell tracking and retrospective cell fate assignment at late somitogenesis stages reveal these cells to be a collection of mono-fated progenitors. Our results suggest that NMps are a conserved population of bipotential progenitors, the lineage of which varies in a species-specific manner due to vastly different rates of differentiation and growth.

Summary A fundamental question in developmental biology is how the early embryo establishes the spatial coordinate system that is later important for the organization of the embryonic body plan. Although we know a lot about the signaling and gene-regulatory networks required for this process, much less is understood about how these can operate to pattern tissues in the context of the extensive cell movements that drive gastrulation. In zebrafish, germ layer specification depends on the inheritance of maternal mRNAs [ 1 , 2 , 3 ], cortical rotation to generate a dorsal pole of β-catenin activity [ 4 , 5 , 6 , 7 , 8 ], and the release of Nodal signals from the yolk syncytial layer (YSL) [ 9 , 10 , 11 , 12 ]. To determine whether germ layer specification is robust to altered cell-to-cell positioning, we separated embryonic cells from the yolk and allowed them to develop as spherical aggregates. These aggregates break symmetry autonomously to form elongated structures with an anterior-posterior pattern. Both forced reaggregation and endogenous cell mixing reveals how robust early axis specification is to spatial disruption of maternal pre-patterning. During these movements, a pole of Nodal signaling emerges that is required for explant elongation via the planar cell polarity (PCP) pathway. Blocking of PCP-dependent elongation disrupts the shaping of opposing poles of BMP and Wnt/TCF activity and the anterior-posterior patterning of neural tissue. These results lead us to suggest that embryo elongation plays a causal role in timing the exposure of cells to changes in BMP and Wnt signal activity during zebrafish gastrulation. Video Abstract

Since publication, an error has been identified in Figure S1C. In the initial production of this figure, we had mistakenly duplicated the column under the heading ''L15 + 3% FBS'' to the left of ''L15 + 10% FBS.'' We have removed the second L15 + 3% FBS column to resolve this image duplication. We also duplicated images at 5 hpc L15 +3% FBS and L15 + 10% FBS. We have checked the metadata and origin of this image and confirmed it originates from the L15 + 10% FBS condition. As this error occurred in figure production and not during data analysis, this error has not impacted the conclusions of this experiment. This error has now been corrected online. The authors apologize for this error and any confusion it may have caused.

Abstract:2 During gastrulation, embryonic cells become specified into distinct germ layers. In mouse, 15All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Over the past decade, evidence has identified a link between protein aggregation, RNA biology, and a subset of degenerative diseases. An important feature of these disorders is the cytoplasmic or nuclear aggregation of RNA-binding proteins (RBPs). Redistribution of RBPs, such as the human TAR DNA-binding 43 protein (TDP-43) from the nucleus to cytoplasmic inclusions is a pathological feature of several diseases. Indeed, sporadic and familial forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration share as hallmarks ubiquitin-positive inclusions. Recently, the wide spectrum of neurodegenerative diseases characterized by RBPs functions’ alteration and loss was collectively named proteinopathies. Here, we show that TBPH (TAR DNA-binding protein-43 homolog), the Drosophila ortholog of human TDP-43 TAR DNA-binding protein-43, interacts with the arcRNA hsrω and with hsrω-associated hnRNPs. Additionally, we found that the loss of the omega speckles remodeler ISWI (Imitation SWI) changes the TBPH sub-cellular localization to drive a TBPH cytoplasmic accumulation. Our results, hence, identify TBPH as a new component of omega speckles and highlight a role of chromatin remodelers in hnRNPs nuclear compartmentalization.

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A fundamental question in developmental biology is how the early embryo breaks initial symmetry to establish the spatial coordinate system later important for the organisation of the embryonic body plan. In zebrafish, this is thought to depend on the inheritance of maternal mRNAs [1][2][3], cortical rotation to generate a dorsal pole of beta-catenin activity [4][5][6][7][8] and the release of Nodal signals from the yolk syncytial layer (YSL) [9][10][11][12]. Recent work aggregating mouse embryonic stem cells has shown that symmetry breaking can occur in the absence of extra-embryonic tissue [19,20]. To test whether this is also true in zebrafish, we separated embryonic cells from the yolk and allowed them to develop as aggregates. These aggregates break symmetry autonomously to form elongated structures with an anterior-posterior pattern. Extensive cell mixing shows that any pre-existing asymmetry is lost prior to the breaking morphological symmetry, revealing that the maternal pre-pattern is not strictly required for early embryo patterning. Following early signalling events after isolation of embryonic cells reveals that a pole of Nodal activity precedes and is required for elongation. The blocking of PCP-dependent convergence and extension movements disrupts the establishment of opposing poles of BMP and Wnt/TCF activity and the patterning of anterior-posterior neural tissue. These results lead us to suggest that convergence and extension plays a causal role in the establishment of morphogen gradients and pattern formation during zebrafish gastrulation.Our current understanding of pattern formation during early development relies heavily on the notion of opposing signalling gradients that set-up rudimentary body plans [17]. These gradients establish cell fates in space that in turn lead to the population specific cell behaviours that dictate the complex cell and tissue rearrangement of gastrulation and axial elongation. In zebrafish, opposing Nodal and BMP signalling gradients are thought to be necessary and su cient for the establishment of the body plan as shown by experiments in which deployment of such gradients in animal caps leads to the formation of a complete AP axis [13]. In addition to controlling cell fate assignments, a recent study has demonstrated that Nodal signalling is a key driver of convergence and extension movements and is su cient to generate these behaviours when expressed within zebrafish animal caps [14]. Furthermore, BMP levels have been shown to be important for controlling cell movements during both gastrulation [21] and posterior body elongation [22]. These observations raise the possibility that opposing BMP and nodal signalling gradients are upstream of both morphogenesis and patterning. However, the causal relationships of these processes are di cult to dissociate in situations where continuous external signalling sources are present, either from overexpression experiments or from the extra-embryonic signals present during early development. To follow how cells can develop and p...

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