Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

Yvette G. Langdon, Ricardo Fuentes, Hong Zhang, Elliott W. Abrams, Florence L. Marlow, Mary C. Mullins

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The vertebrate embryonic dorsoventral axis is established and patterned by Wnt and bone morphogenetic protein (BMP) signaling pathways, respectively. Whereas Wnt signaling establishes the dorsal side of the embryo and induces the dorsal organizer, a BMP signaling gradient patterns tissues along the dorsoventral axis. Early Wnt signaling is provided maternally, whereas BMP ligand expression in the zebrafish is zygotic, but regulated by maternal factors. Concomitant with BMP activity patterning dorsoventral axial tissues, the embryo also undergoes dramatic morphogenetic processes, including the cell movements of gastrulation, epiboly and dorsal convergence. Although the zygotic regulation of these cell migration processes is increasingly understood, far less is known of the maternal regulators of these processes. Similarly, the maternal regulation of dorsoventral patterning, and in particular the maternal control of ventral tissue specification, is poorly understood. We identified split top, a recessive maternal-effect zebrafish mutant that disrupts embryonic patterning upstream of endogenous BMP signaling. Embryos from split top mutant females exhibit a dorsalized embryonic axis, which can be rescued by BMP misexpression or by derepressing endogenous BMP signaling. In addition to dorsoventral patterning defects, split top mutants display morphogenesis defects that are both BMP dependent and independent. These morphogenesis defects include incomplete dorsal convergence, delayed epiboly progression and an early lysis phenotype during gastrula stages. The latter two morphogenesis defects are associated with disruption of the actin and microtubule cytoskeleton within the yolk cell and defects in the outer enveloping cell layer, which are both known mediators of epiboly movements. Through chromosomal mapping and RNA sequencing analysis, we identified the lysosomal endopeptidase cathepsin Ba (ctsba) as the gene deficient in split top embryos. Our results identify a novel role for Ctsba in morphogenesis and expand our understanding of the maternal regulation of dorsoventral patterning.

Original languageEnglish (US)
Pages (from-to)1016-1028
Number of pages13
JournalDevelopment (Cambridge)
Volume143
Issue number6
DOIs
StatePublished - Mar 15 2016

Fingerprint

Cathepsin B
Bone Morphogenetic Proteins
Morphogenesis
Mothers
Embryonic Structures
Zebrafish
Cell Movement
RNA Sequence Analysis
Nuclear RNA
Gastrula
Cathepsins
Endopeptidases
Gastrulation
Actin Cytoskeleton
Microtubules
Vertebrates
Ligands
Phenotype

Keywords

  • BMP
  • Cathepsin B
  • Dorsoventral
  • Maternal effect
  • Morphogenesis
  • Zebrafish

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Langdon, Y. G., Fuentes, R., Zhang, H., Abrams, E. W., Marlow, F. L., & Mullins, M. C. (2016). Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis. Development (Cambridge), 143(6), 1016-1028. https://doi.org/10.1242/dev.128900

Split top : A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis. / Langdon, Yvette G.; Fuentes, Ricardo; Zhang, Hong; Abrams, Elliott W.; Marlow, Florence L.; Mullins, Mary C.

In: Development (Cambridge), Vol. 143, No. 6, 15.03.2016, p. 1016-1028.

Research output: Contribution to journalArticle

Langdon, YG, Fuentes, R, Zhang, H, Abrams, EW, Marlow, FL & Mullins, MC 2016, 'Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis', Development (Cambridge), vol. 143, no. 6, pp. 1016-1028. https://doi.org/10.1242/dev.128900
Langdon YG, Fuentes R, Zhang H, Abrams EW, Marlow FL, Mullins MC. Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis. Development (Cambridge). 2016 Mar 15;143(6):1016-1028. https://doi.org/10.1242/dev.128900
Langdon, Yvette G. ; Fuentes, Ricardo ; Zhang, Hong ; Abrams, Elliott W. ; Marlow, Florence L. ; Mullins, Mary C. / Split top : A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis. In: Development (Cambridge). 2016 ; Vol. 143, No. 6. pp. 1016-1028.
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