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  1. Article ; Online: Different Ectopic Hoxa2 Expression Levels in Mouse Cranial Neural Crest Cells Result in Distinct Craniofacial Anomalies and Homeotic Phenotypes

    Taro Kitazawa / Maryline Minoux / Sebastien Ducret / Filippo M. Rijli

    Journal of Developmental Biology, Vol 10, Iss 9, p

    2022  Volume 9

    Abstract: Providing appropriate positional identity and patterning information to distinct rostrocaudal subpopulations of cranial neural crest cells (CNCCs) is central to vertebrate craniofacial morphogenesis. Hox genes are not expressed in frontonasal and first ... ...

    Abstract Providing appropriate positional identity and patterning information to distinct rostrocaudal subpopulations of cranial neural crest cells (CNCCs) is central to vertebrate craniofacial morphogenesis. Hox genes are not expressed in frontonasal and first pharyngeal arch (PA1) CNCCs, whereas a single Hox gene, Hoxa2 , is necessary to provide patterning information to second pharyngeal arch (PA2) CNCCs. In frog, chick and mouse embryos, ectopic expression of Hoxa2 in Hox -negative CNCCs induced hypoplastic phenotypes of CNCC derivatives of variable severity, associated or not with homeotic transformation of a subset of PA1 structures into a PA2-like identity. Whether these different morphological outcomes are directly related to distinct Hoxa2 overexpression levels is unknown. To address this issue, we selectively induced Hoxa2 overexpression in mouse CNCCs, using a panel of mouse lines expressing different Hoxa2 ectopic expression levels, including a newly generated Hoxa2 knocked-in mouse line. While ectopic Hoxa2 expression at only 60% of its physiological levels was sufficient for pinna duplication, ectopic Hoxa2 expression at 100% of its normal level was required for complete homeotic repatterning of a subset of PA1 skeletal elements into a duplicated set of PA2-like elements. On the other hand, ectopic Hoxa2 overexpression at non-physiological levels (200% of normal levels) led to an almost complete loss of craniofacial skeletal structures. Moreover, ectopic Hoxa5 overexpression in CNCCs, while also resulting in severe craniofacial defects, did not induce homeotic changes of PA1-derived CNCCs, indicating Hoxa2 specificity in repatterning a subset of Hox -negative CNCCs. These results reconcile some discrepancies in previously published experiments and indicate that distinct subpopulations of CNCCs are differentially sensitive to ectopic levels of Hox expression.
    Keywords Hox genes ; Hoxa2 ; Hoxa5 ; cranial neural crest cells ; gain-of-function ; craniofacial morphogenesis ; Biology (General) ; QH301-705.5
    Subject code 616
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: A multiple super-enhancer region establishes inter-TAD interactions and controls Hoxa function in cranial neural crest

    Sandra Kessler / Maryline Minoux / Onkar Joshi / Yousra Ben Zouari / Sebastien Ducret / Fiona Ross / Nathalie Vilain / Adwait Salvi / Joachim Wolff / Hubertus Kohler / Michael B. Stadler / Filippo M. Rijli

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 22

    Abstract: Abstract Enhancer-promoter interactions preferentially occur within boundary-insulated topologically associating domains (TADs), limiting inter-TAD interactions. Enhancer clusters in linear proximity, termed super-enhancers (SEs), ensure high target gene ...

    Abstract Abstract Enhancer-promoter interactions preferentially occur within boundary-insulated topologically associating domains (TADs), limiting inter-TAD interactions. Enhancer clusters in linear proximity, termed super-enhancers (SEs), ensure high target gene expression levels. Little is known about SE topological regulatory impact during craniofacial development. Here, we identify 2232 genome-wide putative SEs in mouse cranial neural crest cells (CNCCs), 147 of which target genes establishing CNCC positional identity during face formation. In second pharyngeal arch (PA2) CNCCs, a multiple SE-containing region, partitioned into Hoxa Inter-TAD Regulatory Element 1 and 2 (HIRE1 and HIRE2), establishes long-range inter-TAD interactions selectively with Hoxa2, that is required for external and middle ear structures. HIRE2 deletion in a Hoxa2 haploinsufficient background results in microtia. HIRE1 deletion phenocopies the full homeotic Hoxa2 knockout phenotype and induces PA3 and PA4 CNCC abnormalities correlating with Hoxa2 and Hoxa3 transcriptional downregulation. Thus, SEs can overcome TAD insulation and regulate anterior Hoxa gene collinear expression in a CNCC subpopulation-specific manner during craniofacial development.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Comparative analysis of Hmx expression and the distribution of neuronal somata in the trigeminal ganglion in lamprey and shark

    Motoki Tamura / Ryota Ishikawa / Yuki Nakanishi / Juan Pascual-Anaya / Makiko Fukui / Takashi Saitou / Fumiaki Sugahara / Filippo M. Rijli / Shigeru Kuratani / Daichi G. Suzuki / Yasunori Murakami

    Zoological Letters, Vol 9, Iss 1, Pp 1-

    insights into the homology of the trigeminal nerve branches and the evolutionary origin of the vertebrate jaw

    2023  Volume 14

    Abstract: Abstract The evolutionary origin of the jaw remains one of the most enigmatic events in vertebrate evolution. The trigeminal nerve is a key component for understanding jaw evolution, as it plays a crucial role as a sensorimotor interface for the ... ...

    Abstract Abstract The evolutionary origin of the jaw remains one of the most enigmatic events in vertebrate evolution. The trigeminal nerve is a key component for understanding jaw evolution, as it plays a crucial role as a sensorimotor interface for the effective manipulation of the jaw. This nerve is also found in the lamprey, an extant jawless vertebrate. The trigeminal nerve has three major branches in both the lamprey and jawed vertebrates. Although each of these branches was classically thought to be homologous between these two taxa, this homology is now in doubt. In the present study, we compared expression patterns of Hmx, a candidate genetic marker of the mandibular nerve (rV3, the third branch of the trigeminal nerve in jawed vertebrates), and the distribution of neuronal somata of trigeminal nerve branches in the trigeminal ganglion in lamprey and shark. We first confirmed the conserved expression pattern of Hmx1 in the shark rV3 neuronal somata, which are distributed in the caudal part of the trigeminal ganglion. By contrast, lamprey Hmx genes showed peculiar expression patterns, with expression in the ventrocaudal part of the trigeminal ganglion similar to Hmx1 expression in jawed vertebrates, which labeled the neuronal somata of the second branch. Based on these results, we propose two alternative hypotheses regarding the homology of the trigeminal nerve branches, providing new insights into the evolutionary origin of the vertebrate jaw.
    Keywords Lamprey ; Shark ; Trigeminal nerve ; Craniofacial development ; Evolution ; Zoology ; QL1-991
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch

    Janine M Daum / Özkan Keles / Sjoerd JB Holwerda / Hubertus Kohler / Filippo M Rijli / Michael Stadler / Botond Roska

    eLife, Vol

    2017  Volume 6

    Abstract: High-resolution daylight vision is mediated by cone photoreceptors. The molecular program responsible for the formation of their light sensor, the outer segment, is not well understood. We correlated daily changes in ultrastructure and gene expression in ...

    Abstract High-resolution daylight vision is mediated by cone photoreceptors. The molecular program responsible for the formation of their light sensor, the outer segment, is not well understood. We correlated daily changes in ultrastructure and gene expression in postmitotic mouse cones, between birth and eye opening, using serial block-face electron microscopy (EM) and RNA sequencing. Outer segments appeared rapidly at postnatal day six and their appearance coincided with a switch in gene expression. The switch affected over 14% of all expressed genes. Genes that switched off were rich in transcription factors and neurogenic genes. Those that switched on contained genes relevant for cone function. Chromatin rearrangements in enhancer regions occurred before the switch was completed, but not after. We provide a resource comprised of correlated EM, RNAseq, and ATACseq data, showing that the growth of a key compartment of a postmitotic cell involves an extensive switch in gene expression and chromatin accessibility.
    Keywords retinal development ; cones ; RNA seq ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2017-11-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A mutant with bilateral whisker to barrel inputs unveils somatosensory mapping rules in the cerebral cortex

    Nicolas Renier / Chloé Dominici / Reha S Erzurumlu / Claudius F Kratochwil / Filippo M Rijli / Patricia Gaspar / Alain Chédotal

    eLife, Vol

    2017  Volume 6

    Abstract: In mammals, tactile information is mapped topographically onto the contralateral side of the brain in the primary somatosensory cortex (S1). In this study, we describe Robo3 mouse mutants in which a sizeable fraction of the trigemino-thalamic inputs ... ...

    Abstract In mammals, tactile information is mapped topographically onto the contralateral side of the brain in the primary somatosensory cortex (S1). In this study, we describe Robo3 mouse mutants in which a sizeable fraction of the trigemino-thalamic inputs project ipsilaterally rather than contralaterally. The resulting mixture of crossed and uncrossed sensory inputs creates bilateral whisker maps in the thalamus and cortex. Surprisingly, these maps are segregated resulting in duplication of whisker representations and doubling of the number of barrels without changes in the size of S1. Sensory deprivation shows competitive interactions between the ipsi/contralateral whisker maps. This study reveals that the somatosensory system can form a somatotopic map to integrate bilateral sensory inputs, but organizes the maps in a different way from that in the visual or auditory systems. Therefore, while molecular pre-patterning constrains their orientation and position, preservation of the continuity of inputs defines the layout of the somatosensory maps.
    Keywords barrel cortex ; Robo3 ; plasticity ; roundabout ; Slit ; Robo ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2017-03-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Activity-dependent death of transient Cajal-Retzius neurons is required for functional cortical wiring

    Martina Riva / Ioana Genescu / Chloé Habermacher / David Orduz / Fanny Ledonne / Filippo M Rijli / Guillermina López-Bendito / Eva Coppola / Sonia Garel / Maria Cecilia Angulo / Alessandra Pierani

    eLife, Vol

    2019  Volume 8

    Abstract: Programmed cell death and early activity contribute to the emergence of functional cortical circuits. While most neuronal populations are scaled-down by death, some subpopulations are entirely eliminated, raising the question of the importance of such ... ...

    Abstract Programmed cell death and early activity contribute to the emergence of functional cortical circuits. While most neuronal populations are scaled-down by death, some subpopulations are entirely eliminated, raising the question of the importance of such demise for cortical wiring. Here, we addressed this issue by focusing on Cajal-Retzius neurons (CRs), key players in cortical development that are eliminated in postnatal mice in part via Bax-dependent apoptosis. Using Bax-conditional mutants and CR hyperpolarization, we show that the survival of electrically active subsets of CRs triggers an increase in both dendrite complexity and spine density of upper layer pyramidal neurons, leading to an excitation/inhibition imbalance. The survival of these CRs is induced by hyperpolarization, highlighting an interplay between early activity and neuronal elimination. Taken together, our study reveals a novel activity-dependent programmed cell death process required for the removal of transient immature neurons and the proper wiring of functional cortical circuits.
    Keywords apoptosis ; neuronal activity ; cortical development ; excitation/inhibition ratio ; Cajal-Retzius neurons ; transient ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2019-12-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Postmitotic Hoxa5 Expression Specifies Pontine Neuron Positional Identity and Input Connectivity of Cortical Afferent Subsets

    Upasana Maheshwari / Dominik Kraus / Nathalie Vilain / Sjoerd J.B. Holwerda / Vanja Cankovic / Nicola A. Maiorano / Hubertus Kohler / Daisuke Satoh / Markus Sigrist / Silvia Arber / Claudius F. Kratochwil / Thomas Di Meglio / Sebastien Ducret / Filippo M. Rijli

    Cell Reports, Vol 31, Iss 11, Pp 107767- (2020)

    2020  

    Abstract: Summary: The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are ... ...

    Abstract Summary: The mammalian precerebellar pontine nucleus (PN) has a main role in relaying cortical information to the cerebellum. The molecular determinants establishing ordered connectivity patterns between cortical afferents and precerebellar neurons are largely unknown. We show that expression of Hox5 transcription factors is induced in specific subsets of postmitotic PN neurons at migration onset. Hox5 induction is achieved by response to retinoic acid signaling, resulting in Jmjd3-dependent derepression of Polycomb chromatin and 3D conformational changes. Hoxa5 drives neurons to settle posteriorly in the PN, where they are monosynaptically targeted by cortical neuron subsets mainly carrying limb somatosensation. Furthermore, Hoxa5 postmigratory ectopic expression in PN neurons is sufficient to attract cortical somatosensory inputs regardless of position and avoid visual afferents. Transcriptome analysis further suggests that Hoxa5 is involved in circuit formation. Thus, Hoxa5 coordinates postmitotic specification, migration, settling position, and sub-circuit assembly of PN neuron subsets in the cortico-cerebellar pathway.
    Keywords Hox transcription factor ; corticopontine circuit development ; precerebellar neurons ; retinoic acid ; neuronal positional identity ; somatosensory topographic connectivity map ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Vitamin A Prevents Inner Ear Defects in Mice with Congenital Homeobox Gene Deficiency

    Massimo Pasqualetti / Filippo M. Rijli

    The Scientific World Journal, Vol 1, Pp 916-

    2001  Volume 918

    Keywords Science (General) ; Q1-390
    Language English
    Publishing date 2001-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: DPP9 enzyme activity controls survival of mouse migratory tongue muscle progenitors and its absence leads to neonatal lethality due to suckling defect

    Kim, Munkyung / Alessandro Piaia / Benjamin Kueng / Berangere Gapp / Corinne Haller / Delphine Weber / Filippo M. Rijli / Frederic Bassilana / Iwona Ksiazek / Johann Wirsching / Kenji Namoto / Maryline Minoux / Samuel Barbieri / Thorsten Lorenz / William Dietrich

    Developmental biology. 2017 Nov. 15, v. 431, no. 2

    2017  

    Abstract: Dipeptidyl peptidase 9 (DPP9) is an intracellular N-terminal post-proline-cleaving enzyme whose physiological function remains largely unknown. We investigated the role of DPP9 enzyme in vivo by characterizing knock-in mice expressing a catalytically ... ...

    Abstract Dipeptidyl peptidase 9 (DPP9) is an intracellular N-terminal post-proline-cleaving enzyme whose physiological function remains largely unknown. We investigated the role of DPP9 enzyme in vivo by characterizing knock-in mice expressing a catalytically inactive mutant form of DPP9 (S729A; DPP9ki/ki mice). We show that DPP9ki/ki mice die within 12–18h after birth. The neonatal lethality can be rescued by manual feeding, indicating that a suckling defect is the primary cause of neonatal lethality. The suckling defect results from microglossia, and is characterized by abnormal formation of intrinsic muscles at the distal tongue. In DPP9ki/ki mice, the number of occipital somite-derived migratory muscle progenitors, forming distal tongue intrinsic muscles, is reduced due to increased apoptosis. In contrast, intrinsic muscles of the proximal tongue and extrinsic tongue muscles, which derive from head mesoderm, develop normally in DPP9ki/ki mice. Thus, lack of DPP9 activity in mice leads to impaired tongue development, suckling defect and subsequent neonatal lethality due to impaired survival of a specific subset of migratory tongue muscle progenitors.
    Keywords apoptosis ; enzyme activity ; head ; mice ; mortality ; muscles ; mutants ; suckling ; tongue
    Language English
    Dates of publication 2017-1115
    Size p. 297-308.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1114-9
    ISSN 1095-564X ; 0012-1606
    ISSN (online) 1095-564X
    ISSN 0012-1606
    DOI 10.1016/j.ydbio.2017.09.001
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Prenatal thalamic waves regulate cortical area size prior to sensory processing

    Verónica Moreno-Juan / Anton Filipchuk / Noelia Antón-Bolaños / Cecilia Mezzera / Henrik Gezelius / Belen Andrés / Luis Rodríguez-Malmierca / Rafael Susín / Olivier Schaad / Takuji Iwasato / Roland Schüle / Michael Rutlin / Sacha Nelson / Sebastien Ducret / Miguel Valdeolmillos / Filippo M. Rijli / Guillermina López-Bendito

    Nature Communications, Vol 8, Iss 1, Pp 1-

    2017  Volume 14

    Abstract: How sensory maps are formed in the brain is only partially understood. Here the authors describe spontaneous calcium waves that propagate across different sensory nuclei in the embryonic thalamus; disrupting the wave pattern triggers thalamic gene ... ...

    Abstract How sensory maps are formed in the brain is only partially understood. Here the authors describe spontaneous calcium waves that propagate across different sensory nuclei in the embryonic thalamus; disrupting the wave pattern triggers thalamic gene expression changes and eventually alters the size of cortical areas.
    Keywords Science ; Q
    Language English
    Publishing date 2017-02-01T00:00:00Z
    Publisher Nature Portfolio
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