{"title":"The RNF220 domain nuclear factor Teyrha-Meyrha (Tey) regulates the migration and differentiation of specific visceral and somatic muscles in Drosophila","authors":"M. Frasch, Afshan Ismat, I. Reim, J. Raufer","doi":"10.1101/2022.11.18.517102","DOIUrl":"https://doi.org/10.1101/2022.11.18.517102","url":null,"abstract":"The development of the visceral musculature of the Drosophila midgut encompasses a closely coordinated sequence of migration events of cells from the trunk and caudal visceral mesoderm, respectively, that underlies the formation of the stereotypic orthogonal pattern of circular and longitudinal midgut muscles. Our current study focuses on the last step of migration and morphogenesis of the longitudinal visceral muscle precursors derived from the caudal mesoderm. We show that these multinucleated muscle precursors utilize dynamic filopodial extensions to migrate in dorsal and ventral directions over the forming midgut tube. The establishment of maximal dorsoventral distances from one another and subsequent alignment with their anteroposterior neighbors leads to the equidistant coverage of the midgut with longitudinal muscle fibers. We identify Teyrha-Meyhra (Tey), a tissue-specific nuclear factor related to the RNF220 domain protein family, as a crucial regulator of this process of muscle migration and morphogenesis that is further required for proper differentiation of the longitudinal visceral muscles. In addition, Tey is expressed in a single type of somatic muscle founder cell in each hemisegment. Tey regulates the migration of this founder cell and is required for the proper pathfinding of its developing myotube to specific myotendinous attachment sites.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80125457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara J Knowles, April M Stafford, Tariq Zaman, K. Angara, Michael R. Williams, J. Newbern, D. Vogt
{"title":"Distinct hyperactive RAS/MAPK alleles converge on common GABAergic interneuron core programs","authors":"Sara J Knowles, April M Stafford, Tariq Zaman, K. Angara, Michael R. Williams, J. Newbern, D. Vogt","doi":"10.1101/2022.08.04.502867","DOIUrl":"https://doi.org/10.1101/2022.08.04.502867","url":null,"abstract":"RAS/MAPK gene dysfunction underlies various cancers and neurocognitive disorders. While the role of RAS/MAPK genes have been well studied in cancer, less is known about their function during neurodevelopment. There are many genes that work in concert to regulate RAS/MAPK signaling, suggesting that if common brain phenotypes could be discovered they could have a broad impact on the many other disorders caused by distinct RAS/MAPK genes. We assessed the cellular and molecular consequences of hyperactivating the RAS/MAPK pathway using two distinct genes in a cell type previously implicated in RAS/MAPK-mediated cognitive changes, cortical GABAergic interneurons. We uncovered some GABAergic core programs that are commonly altered in each of the mutants. Notably, hyperactive RAS/MAPK mutants bias developing cortical interneurons towards those that are somatostatin+. The increase in somatostatin+ interneurons could also be induced by elevated neural activity and we show the core RAS/MAPK signaling pathway is one mechanism by which this occurs. Overall, these findings present new insights into how different RAS/MAPK mutations can converge on GABAergic interneurons, which may be important for other RAS/MAPK genes/disorders.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91368675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zainab Afzal, Jeffrey J. Lange, Christof Nolte, S. McKinney, Christopher Wood, Ariel Paulson, Bony De Kumar, J. Unruh, Brian D. Slaughter, R. Krumlauf
{"title":"Shared retinoic acid responsive enhancers coordinately regulate nascent transcription of Hoxb coding and non-coding RNAs in the developing mouse neural tube","authors":"Zainab Afzal, Jeffrey J. Lange, Christof Nolte, S. McKinney, Christopher Wood, Ariel Paulson, Bony De Kumar, J. Unruh, Brian D. Slaughter, R. Krumlauf","doi":"10.1101/2022.08.30.505933","DOIUrl":"https://doi.org/10.1101/2022.08.30.505933","url":null,"abstract":"Signaling pathways regulate the patterns of Hox gene expression that underlie their functions in specification of axial identity. Little is known about the properties of cis-regulatory elements and underlying transcriptional mechanisms that integrate graded signaling inputs to coordinately control Hox expression. Here we optimized single molecule fluorescent in situ hybridization (smFISH) technique with probes spanning introns to evaluate how three shared retinoic acid response element (RARE)-dependent enhancers in the Hoxb cluster regulate patterns of nascent transcription in vivo at the level of single cells in wild type and mutant embryos. We predominately detect nascent transcription of only a single Hoxb gene in each cell, with no evidence for simultaneous co-transcriptional coupling of all or specific subsets of genes. Single and/or compound RARE mutations indicate each enhancer differentially impacts global and local patterns of nascent transcription, suggesting that selectivity and competitive interactions between these enhancers is important to robustly maintain the proper levels and patterns of nascent Hoxb transcription. This implies rapid and dynamic regulatory interactions potentiate transcription of genes through combined inputs from these enhancers in coordinating the RA response.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74497062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epidermal growth factor receptor signaling protects epithelia from morphogenetic instability and tissue damage in Drosophila","authors":"Kentaro Yoshida, S. Hayashi","doi":"10.1101/2022.08.28.505615","DOIUrl":"https://doi.org/10.1101/2022.08.28.505615","url":null,"abstract":"Dying cells in the epithelia communicate with neighboring cells to initiate coordinated cell removal to maintain epithelial integrity. Naturally occurring apoptotic cells are mostly extruded basally and engulfed by macrophages. Here, we investigated the role of Epidermal growth factor (EGF) receptor (EGFR) signaling in the maintenance of epithelial homeostasis. In Drosophila embryos, epithelial tissues undergoing groove formation preferentially enhanced extracellular signal-regulated kinases (ERK) signaling. In EGFR mutant embryos at stage 11, sporadic apical cell extrusion in the head initiates a cascade of apical extrusions of apoptotic and non-apoptotic cells that sweeps the entire ventral body wall. Here, we showed that clustered apoptosis, groove formation, and wounding sensitized EGFR mutant epithelia to initiate massive tissue disintegration. We further showed that tissue detachment from the vitelline membrane, which frequently occurs during morphogenetic processes, is a key trigger for the EGFR mutant phenotype. These findings indicate that, in addition to cell survival, EGFR plays a role in maintaining epithelial integrity, which is essential for protecting tissues from transient instability caused by morphogenetic movement and damage.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"2015 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87074026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Krup, Sarah Winchester, Sanjeev S. Ranade, Ayushi Agrawal, W. Devine, Tanvi Sinha, Krishna Choudhary, Martin H. Dominguez, Reuben Thomas, B. Black, D. Srivastava, B. Bruneau
{"title":"A Mesp1-dependent developmental breakpoint in transcriptional and epigenomic specification of early cardiac precursors","authors":"A. Krup, Sarah Winchester, Sanjeev S. Ranade, Ayushi Agrawal, W. Devine, Tanvi Sinha, Krishna Choudhary, Martin H. Dominguez, Reuben Thomas, B. Black, D. Srivastava, B. Bruneau","doi":"10.1101/2022.08.22.504863","DOIUrl":"https://doi.org/10.1101/2022.08.22.504863","url":null,"abstract":"Transcriptional networks governing cardiac precursor cell (CPC) specification are incompletely understood due in part to limitations in distinguishing CPCs from non-cardiac mesoderm in early gastrulation. We leveraged detection of early cardiac lineage transgenes within a granular single cell transcriptomic time course of mouse embryos to identify emerging CPCs and describe their transcriptional profiles. Mesp1, a transiently-expressed mesodermal transcription factor (TF), is canonically described as an early regulator of cardiac specification. However, we observed perdurance of CPC transgene-expressing cells in Mesp1 mutants, albeit mis-localized, prompting us to investigate the scope of Mesp1’s role in CPC emergence and differentiation. Mesp1 mutant CPCs failed to robustly activate markers of cardiomyocyte maturity and critical cardiac TFs, yet they exhibited transcriptional profiles resembling cardiac mesoderm progressing towards cardiomyocyte fates. Single cell chromatin accessibility analysis defined a Mesp1-dependent developmental breakpoint in cardiac lineage progression at a shift from mesendoderm transcriptional networks to those necessary for cardiac patterning and morphogenesis. These results reveal Mesp1-independent aspects of early CPC specification and underscore a Mesp1-dependent regulatory landscape required for progression through cardiogenesis.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84822195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Owen, J. Rainger, Hemant Bengani, F. Kilanowski, David R FitzPatrick, A. Papanastasiou
{"title":"Characterization of an eye field-like state during optic vesicle organoid development","authors":"L. Owen, J. Rainger, Hemant Bengani, F. Kilanowski, David R FitzPatrick, A. Papanastasiou","doi":"10.1101/2022.08.16.504119","DOIUrl":"https://doi.org/10.1101/2022.08.16.504119","url":null,"abstract":"Specification of the eye field (EF) within the neural plate marks the earliest detectable stage of eye development. Experimental evidence, primarily from non-mammalian model systems, indicates that the stable formation of this group of cells requires the activation of a set of key transcription factors (TFs). This critical event is challenging to probe in mammals and, quantitatively, little is known regarding the regulation of the transition of cells to this ocular fate. Using optic vesicle organoids to model the onset of the EF, we generate timecourse transcriptomic data allowing us to identify dynamic gene-expression programs that characterise this cellular-state transition. Integrating this with chromatin accessibility data suggests a direct role of canonical EFTFs in regulating these gene-expression changes, and high-lights candidate cis-regulatory elements through which these TFs act. Finally, we begin to test a subset of these candidate enhancer elements, within the organoid system, by perturbing the underlying DNA sequence and measuring transcriptomic changes during EF activation.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80844626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yushi T. Redhead, Dorota Gibbins, Eva Lana‐Elola, Sheona Watson-Scales, Lisa Dobson, M. Krause, Karen J. Liu, E. Fisher, Jeremy B. A. Green, V. Tybulewicz
{"title":"Craniofacial dysmorphology in Down syndrome is caused by increased dosage of Dyrk1a and at least three other genes","authors":"Yushi T. Redhead, Dorota Gibbins, Eva Lana‐Elola, Sheona Watson-Scales, Lisa Dobson, M. Krause, Karen J. Liu, E. Fisher, Jeremy B. A. Green, V. Tybulewicz","doi":"10.1101/2022.06.27.497841","DOIUrl":"https://doi.org/10.1101/2022.06.27.497841","url":null,"abstract":"Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), occurs in 1 in 800 live births and is the most common human aneuploidy. DS results in multiple phenotypes, including craniofacial dysmorphology, characterised by midfacial hypoplasia, brachycephaly and micrognathia. The genetic and developmental causes of this are poorly understood. Using morphometric analysis of the Dp1Tyb mouse model of DS and an associated genetic mouse genetic mapping panel, we demonstrate that four Hsa21-orthologous regions of mouse chromosome 16 contain dosage-sensitive genes that cause the DS craniofacial phenotype, and identify one of these causative genes as Dyrk1a. We show that the earliest and most severe defects in Dp1Tyb skulls are in bones of neural crest (NC) origin, and that mineralisation of the Dp1Tyb skull base synchondroses is aberrant. Furthermore, we show that increased dosage of Dyrk1a results in decreased NC cell proliferation and a decrease in size and cellularity of the NC-derived frontal bone primordia. Thus, DS craniofacial dysmorphology is caused by increased dosage of Dyrk1a and at least three other genes. Summary statement Craniofacial dysmorphology in mouse models of Down syndrome is caused by increased dosage of at least four genes including Dyrk1a, resulting in reduced proliferation of neural crest-derived cranial bone progenitors.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"439 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82880737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Santos Teixeira, Thea van den Berg, K. T. ten Tusscher
{"title":"Complementary roles for auxin and auxin signalling revealed by reverse engineering lateral root stable prebranch site formation","authors":"J. Santos Teixeira, Thea van den Berg, K. T. ten Tusscher","doi":"10.1101/2022.06.24.497450","DOIUrl":"https://doi.org/10.1101/2022.06.24.497450","url":null,"abstract":"Priming is the process through which periodic elevations in auxin signalling prepattern future sites for lateral root formation, called prebranch sites. Thusfar is has remained a matter of debate to what extent elevations in auxin concentration and/or auxin signalling are critical for priming and prebranch site formation. Recently, we discovered a reflux-and-growth mechanism for priming generating periodic elevations in auxin concentration that subsequently dissipate. Here we reverse engineer a mechanism for prebranch site formation that translates these transient elevations into a persistent increase in auxin signalling, resolving the prior debate into a two-step process of auxin concentration mediated initial signal and auxin signalling capacity mediated memorization. A critical aspect of the prebranch site formation mechanism is its activation in response to time integrated rather than instantaneous auxin signalling. The proposed mechanism is demonstrated to be consistent with prebranch site auxin signalling dynamics, lateral inhibition and symmetry breaking mechanisms and perturbations in auxin homeostasis. Summary statement Using computational modeling we reveal the likely complementary roles of auxin and auxin signalling in one of the earliest step in the formation of plant lateral roots, prebranch site formation.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89313322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth Bearce, Zoe H. Irons, Samuel B Craig, Colin J. Kuhns, Cynthia Sabazali, Dylan R. Farnsworth, Adam C. Miller, D. Grimes
{"title":"Daw1 regulates the timely onset of cilia motility during development","authors":"Elizabeth Bearce, Zoe H. Irons, Samuel B Craig, Colin J. Kuhns, Cynthia Sabazali, Dylan R. Farnsworth, Adam C. Miller, D. Grimes","doi":"10.1242/dev.200017","DOIUrl":"https://doi.org/10.1242/dev.200017","url":null,"abstract":"ABSTRACT Motile cilia generate cell propulsion and extracellular fluid flows that are crucial for airway clearance, fertility and left-right patterning. Motility is powered by dynein arm complexes that are assembled in the cytoplasm then imported into the cilium. Studies in Chlamydomonas reinhardtii showed that ODA16 is a cofactor which promotes dynein arm import. Here, we demonstrate that the zebrafish homolog of ODA16, Daw1, facilitates the onset of robust cilia motility during development. Without Daw1, cilia showed markedly reduced motility during early development; however, motility subsequently increased to attain close to wild-type levels. Delayed motility onset led to differential effects on early and late cilia-dependent processes. Remarkably, abnormal body axis curves, which formed during the first day of development due to reduced cilia motility, self-corrected when motility later reached wild-type levels. Zebrafish larva therefore possess the ability to survey and correct body shape abnormalities. This work defines Daw1 as a factor which promotes the onset of timely cilia motility and can explain why human patients harboring DAW1 mutations exhibit significant laterality perturbations but mild airway and fertility complications.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"1723 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89261622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Henning J. Falk, Takehito Tomita, Gregor Mönke, K. McDole, A. Aulehla
{"title":"Imaging the onset of oscillatory signaling dynamics during mouse embryo gastrulation","authors":"Henning J. Falk, Takehito Tomita, Gregor Mönke, K. McDole, A. Aulehla","doi":"10.1242/dev.200083","DOIUrl":"https://doi.org/10.1242/dev.200083","url":null,"abstract":"ABSTRACT A fundamental requirement for embryonic development is the coordination of signaling activities in space and time. A notable example in vertebrate embryos is found during somitogenesis, where gene expression oscillations linked to the segmentation clock are synchronized across cells in the presomitic mesoderm (PSM) and result in tissue-level wave patterns. To examine their onset during mouse embryo development, we studied the dynamics of the segmentation clock gene Lfng during gastrulation. To this end, we established an imaging setup using selective plane illumination microscopy (SPIM) that enables culture and simultaneous imaging of up to four embryos (‘SPIM- for-4’). Using SPIM-for-4, combined with genetically encoded signaling reporters, we detected the onset of Lfng oscillations within newly formed mesoderm at presomite stages. Functionally, we found that initial synchrony and the first ∼6-8 oscillation cycles occurred even when Notch signaling was impaired, revealing similarities to previous findings made in zebrafish embryos. Finally, we show that a spatial period gradient is present at the onset of oscillatory activity, providing a potential mechanism accounting for our observation that wave patterns build up gradually over the first oscillation cycles.","PeriodicalId":77105,"journal":{"name":"Development (Cambridge, England). Supplement","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86990106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}