Browsing by Author "Mallo, Moises"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
- Hox genes and regional patterning of the vertebrate body planPublication . Mallo, Moises; Wellik, Deneen M.; Deschamps, JacquelineSeveral decades have passed since the discovery of Hox genes in the fruit fly Drosophila melanogaster. Their unique ability to regulate morphologies along the anteroposterior (AP) axis (Lewis, 1978) earned them well-deserved attention as important regulators of embryonic development. Phenotypes due to loss- and gain-of-function mutations in mouse Hox genes have revealed that the spatio-temporally controlled expression of these genes is critical for the correct morphogenesis of embryonic axial structures. Here, we review recent novel insight into the modalities of Hox protein function in imparting specific identity to anatomical regions of the vertebral column, and in controlling the emergence of these tissues concomitantly with providing them with axial identity. The control of these functions must have been intimately linked to the shaping of the body plan during evolution.
- Isolated Incudostapedial Cholesteatomas: Unique Radiologic and Surgical FeaturesPublication . MacDonald, Bridget; Bommakanti, Krishna; Mallo, Moises; Carvalho, Daniela
- Reorganisation ofHoxdregulatory landscapes during the evolution of a snake-like body planPublication . Guerreiro, Isabel; Gitto, Sandra; Novoa, Ana; Codourey, Julien; Nguyen Huynh, Thi Hanh; Gonzalez, Federico; Milinkovitch, Michel C; Mallo, Moises; Duboule, DenisWithin land vertebrate species, snakes display extreme variations in their body plan, characterized by the absence of limbs and an elongated morphology. Such a particular interpretation of the basic vertebrate body architecture has often been associated with changes in the function or regulation of Hox genes. Here, we use an interspecies comparative approach to investigate different regulatory aspects at the snake HoxD locus. We report that, unlike in other vertebrates, snake mesoderm-specific enhancers are mostly located within the HoxD cluster itself rather than outside. In addition, despite both the absence of limbs and an altered Hoxd gene regulation in external genitalia, the limb-associated bimodal HoxD chromatin structure is maintained at the snake locus. Finally, we show that snake and mouse orthologous enhancer sequences can display distinct expression specificities. These results show that vertebrate morphological evolution likely involved extensive reorganisation at Hox loci, yet within a generally conserved regulatory framework.
- A Tgfbr1/Snai1-dependent developmental module at the core of vertebrate axial elongationPublication . Dias, André; Lozovska, Anastasiia; Wymeersch, Filip J; Nóvoa, Ana; Binagui-Casas, Anahi; Sobral, Daniel; Martins, Gabriel G; Wilson, Valerie; Mallo, Moises
- A tissue-specific, Gata6-driven transcriptional program instructs remodeling of the mature arterial treePublication . Losa, Marta; Latorre, Victor; Andrabi, Munazah; Ladam, Franck; Sagerström, Charles; Novoa, Ana; Zarrineh, Peyman; Bridoux, Laure; Hanley, Neil A; Mallo, Moises; Bobola, NicolettaConnection of the heart to the systemic circulation is a critical developmental event that requires selective preservation of embryonic vessels (aortic arches). However, why some aortic arches regress while others are incorporated into the mature aortic tree remains unclear. By microdissection and deep sequencing in mouse, we find that neural crest (NC) only differentiates into vascular smooth muscle cells (SMCs) around those aortic arches destined for survival and reorganization, and identify the transcription factor Gata6 as a crucial regulator of this process. Gata6 is expressed in SMCs and its target genes activation control SMC differentiation. Furthermore, Gata6 is sufficient to promote SMCs differentiation in vivo, and drive preservation of aortic arches that ought to regress. These findings identify Gata6-directed differentiation of NC to SMCs as an essential mechanism that specifies the aortic tree, and provide a new framework for how mutations in GATA6 lead to congenital heart disorders in humans.
- Two CRISPR/Cas9-mediated methods for targeting complex insertions, deletions, or replacements in mousePublication . Pineault, Kyriel M.; Novoa, Ana; Lozovska, Anastasiia; Wellik, Deneen M.; Mallo, MoisesGenetically modified model organisms are valuable tools for probing gene function, dissecting complex signaling networks, studying human disease, and more. CRISPR/Cas9 technology has significantly democratized and reduced the time and cost of generating genetically modified models to the point that small gene edits are now routinely and efficiently generated in as little as two months. However, generation of larger and more sophisticated gene-modifications continues to be inefficient. Alternative ways to provide the replacement DNA sequence, method of Cas9 delivery, and tethering the template sequence to Cas9 or the guide RNA (gRNA) have all been tested in an effort to maximize homology-directed repair for precise modification of the genome. We present two CRISPR/Cas9 methods that have been used to successfully generate large and complex gene-edits in mouse. In the first method, the Cas9 enzyme is used in conjunction with two sgRNAs and a long single-stranded DNA (lssDNA) template prepared by an alternative protocol. The second method utilizes a tethering approach to couple a biotinylated, double-stranded DNA (dsDNA) template to a Cas9-streptavidin fusion protein. •Alternative method for generating long, single-stranded DNA templates for CRISPR/Cas9 editing.•Demonstration that using two sgRNAs with Cas9-streptavidin/biotinylated-dsDNA is feasible for large DNA modifications.