Top 6 Biorxiv Papers Today in Developmental Biology


1.994 Mikeys
#1. Gli3 loss-of-function compromises vomeronasal neurogenesis, formation of olfactory ensheathing cells in the nasal mucosa, and GnRH-1 neuronal migration
Ed Zandro M Taroc, Ankana Naik, Jennifer M Lin, Nicolas B Peterson, David L Keefe, Elizabet Genis, Gabriele Fuchs, Ravikumar Balasubramanian, Paolo E Forni
Gonadotropin-releasing-hormone-1 neurons (GnRH-1ns) control pubertal onset, and fertility. During mammalian development, GnRH-1ns migrate from the developing vomeronasal organ (VNO) into the brain, where they control the pituitary release of gonadotropins. Loss-of-function of the transcription factor Gli3 disrupts olfactory development, however, if Gli3 plays roles in GnRH-1 neuronal development is unclear. By analyzing Gli3 extra-toe mutants (Gli3Xt/Xt), we found neurogenic defects in the VNO, lack of olfactory ensheathing cells in the nasal mucosa and disrupted GnRH-1 neuronal migration. We discovered that Gli3 loss-of-function impairs the formation of achaete-scute family bHLH transcription factor 1 (Ascl-1) positive vomeronasal progenitors, but not the onset of GnRH-1ns. Moreover, the dysmorphic brain of Gli3Xt/Xt mutants also displayed altered Semaphorin-3A expression, a key guidance cue for GnRH-1 migration. In contrast to Gli3Xt/Xt, Ascl-1null mutants showed reduced neurogenesis for both vomeronasal and GnRH-1ns. The...
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Authors: 9
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1.994 Mikeys
#2. Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse
Feini Qu, Ilan C Palte, Paul M Gontarz, Bo Zhang, Farshid Guilak
Humans have limited regenerative potential of musculoskeletal tissues following limb or digit loss. The murine digit has been used to study mammalian regeneration, where stem/progenitor cells (the 'blastema') regrow the digit tip after distal, but not proximal, amputation. However, the molecular mechanisms responsible for this response remain to be determined. We hypothesized that regeneration is initiated and maintained by a gene regulatory network that recapitulates aspects of limb development, whereas a non-regenerative response exhibits fibrotic wound healing and minimal bone remodeling. To test these hypotheses, we evaluated the spatiotemporal formation of bone and fibrous tissues after level-dependent amputation of the murine terminal phalanx and quantified the transcriptome of the repair tissue. We show that digit regeneration is a level-dependent and spatiotemporally controlled process, with distal and proximal amputations showing significant differences in gene expression and tissue regrowth over time. Regeneration is...
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Authors: 5
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1.994 Mikeys
#3. A terminal selector prevents a Hox transcriptional switch to safeguard motor neuron identity throughout life
Weidong Feng, Yinan Li, Pauline Dao, Jihad Aburas, Priota Islam, Benayahu Elbaz, Anna Kolarzyk, Andre E.X. Brown, Paschalis Kratsios
Nervous system function critically relies on continuous expression of neuron type-specific terminal identity features, such as neurotransmitter receptors, ion channels and neuropeptides. How individual neuron types select such features during development and maintain them throughout life is poorly understood. Here, we report an unconventional mechanism that enables cholinergic motor neurons (MNs) in the C. elegans ventral nerve cord to select and maintain their distinct terminal identity features. The conserved terminal selector UNC-3 (Collier/Ebf) UNC-3 is continuously required not only to promote cholinergic MN features, but also to prevent expression of 'unwanted' terminal identity features normally reserved for other neuron types. Mechanistically, this dual function is achieved by the ability of UNC-3 to prevent a switch in the transcriptional targets of the Hox protein LIN-39 (Scr/Dfd/Hox4-5). The strategy of a terminal selector preventing a Hox transcriptional switch may constitute a general principle for safeguarding...
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1.993 Mikeys
#4. Genome-wide RNAi screen for context-dependent tumor suppressors identified using in vivo models for neoplasia in Drosophila
Casper Groth, Pooja Vaid, Aditi Khatpe, Nelchi Prashali, Avantika Ahiya, Diana Andrejeva, Madhumita Chakladar, Sanket Nagarkar, Rachel Paul, Teresa Eichenlaub, Hector Herranz, TS Sridhar, Stephen Cohen, LS Shashidhara
Genetic approaches in Drosophila have successfully identified many genes involved in regulation of growth control as well as genetic interactions relevant to the initiation and progression of cancer in vivo. Here, we report on large-scale RNAi-based screens to identify potential tumor suppressor genes that interact with known cancer-drivers: The Epidermal Growth Factor Receptor and the Hippo pathway transcriptional cofactor Yorkie. These screens were designed to identify genes whose depletion drove tissue expressing EGFR or Yki from a state of benign overgrowth into neoplastic transformation in vivo. We also report on an independent screen aimed to identify genes whose depletion suppressed formation of neoplastic tumors in an existing EGFR-dependent neoplasia model. Many of the positives identified here are known to be functional in growth control pathways. We also find a number of novel connections to Yki and EGFR driven tissue growth, mostly unique to one of the two. Thus, resources provided here would be useful to all...
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Authors: 14
Total Words: 7857
Unqiue Words: 2475

1.984 Mikeys
#5. Differential chromatin accessibility in developing projection neurons is correlated with transcriptional regulation of cell fate
Whitney E Heavner, Shaoyi Ji, James H Notwell, Ethan S Dyer, Alex M Tseng, Johannes Birgmeier, Boyoung Yoo, Gill Bejerano, Susan K McConnell
We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than fifty unique types of mature cortical projection neurons defined by their distinct gene expression profiles. Here we compare gene expression and chromatin accessibility of two subclasses of projection neurons with divergent morphological and functional features as they develop in the mouse brain between embryonic day 13 and postnatal day 5 in order to identify transcriptional networks that diversity neuron cell fate. We find groups of transcription factors whose expression is correlated with chromatin accessibility, transcription factor binding motifs, and lncRNAs that define each subclass and validate the function of a family of novel candidate genes...
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Authors: 9
Total Words: 14033
Unqiue Words: 3570

1.946 Mikeys
#6. The Clathrin adaptor AP-1 and the Rab-stabilizing chaperone Stratum act in two parallel pathways to control the activation of the Notch pathway in Drosophila
Karen Bellec, Isabelle Gicquel, Roland Le Borgne
Drosophila sensory organ precursors divide asymmetrically to generate pIIa/pIIb cells whose identity relies on the differential activation of Notch during cytokinesis. While Notch is present apically and basally relative to the midbody at the pIIa-pIIb interface, only the basal pool of Notch is reported to contribute to Notch activation in the pIIa cell. Such proper intra-lineage signalling therefore requires appropriate apico-basal targeting of Notch, its ligand Delta and its trafficking partner Sanpodo. We previously reported that AP-1 and Stratum regulate the intracellular trafficking of Notch and Sanpodo from the trans-Golgi network to basolateral membrane. Loss of AP-1 or of Stratum caused mild Notch phenotype. Here, we report that the concomitant loss of AP-1 and Stratum result in the stabilization of the apical pool of Notch, Delta and Spdo, the loss of the basal pool of Notch at the pIIa-pIIb interface, and is associated with activation of Notch in the two SOP daughters. We propose that AP-1 and Stratum control two...
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Authors: 3
Total Words: 6673
Unqiue Words: 2021

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