Biology subjects

Cirio, M. C.

Publications and source records attributed to Cirio, M. C..

3 recordsLinked to original sources

bioRxiv2023

Xenopus Ssbp2 is required for embryonic pronephros morphogenesis and terminal differentiation

The nephron, functional unit of the vertebrate kidney, is specialized in metabolic wastes excretion and body fluids osmoregulation. Given the high evolutionary conservation of gene expression and segmentation patterning between mammalian and amphibian nephrons, the Xenopus laevis pronephric kidney offers a simplified model for studying nephrogenesis. The Lhx1 transcription factor plays several roles during embryogenesis, regulating target genes expression by forming multiprotein complexes with LIM binding protein 1 (Ldb1). However, few Lhx1-Ldb1 cofactors have been identified for kidney organogenesis. By tandem-affinity purification from kidney-induced Xenopus animal caps, we identified single-stranded DNA binding protein 2 (Ssbp2) interacts with the Ldb1-Lhx1 complex. Ssbp2 is expressed in the Xenopus pronephros, and knockdown prevents normal morphogenesis and differentiation of the glomus and the convoluted renal tubules. We demonstrate a role for a member of the Ssbp family in kidney organogenesis and provide evidence of a fundamental function for the Ldb1-Lhx1-Ssbp transcriptional complexes in embryonic development.

developmental biology↗

bioRxiv2021

ANALYSIS OF CHD-7 DEFECTIVE DAUER NEMATODES IMPLICATES COLLAGEN MISREGULATION IN CHARGE SYNDROME FEATURES.

CHARGE syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding protein7 (CHD7) and characterized by retarded growth and malformations in the heart and nervous system. Despite the public health relevance of this disorder, relevant targets of CHD7 that relate to disease pathology are still poorly understood. Here we report that chd-7, the nematode ortholog of Chd7, is required for dauer morphogenesis, lifespan determination, and stress response. Consistent with our discoveries, we found chd-7 to be allelic to scd-3, a previously identified dauer suppressor from the TGF-{beta} pathway. Notably, DAF-12 promoted chd-7 expression, which is necessary to repress daf-9 for execution of the dauer program. Transcriptomic analysis comparing chd-7-defective and normal dauers showed enrichment of collagen genes, consistent with a conserved role for the TGF-{beta} pathway in formation of the extracellular matrix. To validate a conserved function for chd-7 in vertebrates, we used Xenopus laevis embryos, an established model to study craniofacial development. Morpholino mediated knockdown of Chd7 led to a reduction in col2a1 mRNA levels. Both embryonic lethality and craniofacial defects in Chd7-depleted tadpoles were partially rescued by over-expression of col2a1 mRNA. We suggest that pathogenic features of CHARGE syndrome caused by Chd7 mutations, such as craniofacial malformations, result from the reduction of collagen levels, implying that the extracellular matrix might represent a critical target of Chd7 in CHARGE development. SIGNIFICANCE STATEMENTCHARGE Syndrome is a complex developmental disorder caused by mutations in the chromodomain helicase DNA-binding protein-7 (CHD7). Unfortunately, the cellular events that lead to CHARGE syndrome are still poorly understood. In C. elegans, we identified chd-7 in a screen for suppressors of dauer formation, an alternative larval stage that develops in response to sensory signals of a harsh environment. We found that chd-7 regulates expression of collagens, which constitute the worms cuticle, a specialized extracellular matrix. In frogs embryos, we show that Chd7 inhibition leads to poor Col2a1, which is necessary and sufficient to exhibit CHARGE features. These studies establish C. elegans as an amenable animal model to study the etiology of the developmental defects associated with pathogenic Chd7.

genetics↗

bioRxiv2020

Furry is required for cell movements during gastrulation and functionally interacts with NDR1

Gastrulation is a key event in animal embryogenesis during which the germ layers precursors are rearranged and the embryonic axes are established. Cell polarization is essential during gastrulation driving asymmetric cell division, cell movements and cell shape changes. Furry (Fry) gene encodes an evolutionarily conserved protein with a wide variety of cellular functions mostly related to cell polarization and morphogenesis in invertebrates. However, little is known about its function in vertebrate development. Here we show that in Xenopus, Fry participates in the regulation of morphogenetic processes during gastrulation. Using morpholino knock-down, we demonstrate a role of Fry in blastopore closure and dorsal axis elongation. Loss of Fry function drastically affects the movement and morphological polarization of cells during gastrulation, in addition to dorsal mesoderm convergent extension, responsible for head-to-tail elongation. Finally, we demonstrate a functional interaction between Fry and NDR1 kinase, providing evidence of an evolutionarily conserved complex required for morphogenesis.

developmental biology↗